Accurate Prognosis Prediction of Pancreatic Ductal Adenocarcinoma Using Integrated Clinico-Genomic Data of Endoscopic Ultrasound-Guided Fine Needle Biopsy.

The aim of this study was to investigate the clinical utility of minimal specimens acquired from endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and perform targeted deep sequencing as a prognosis prediction tool for pancreatic ductal adenocarcinoma (PDAC). A total of 116 specimens with pathologically confirmed PDAC via EUS-FNB were tested using CancerSCAN® panel for a customized targeted deep sequencing. Clinical prognostic factors significantly associated with survival in PDACs were as follows: stage, tumor mass size, tumor location, metastasis, chemotherapy, and initial CA19-9 level. A total of 114 patients (98.3%) had at least a single genetic alteration, and no mutations were detected in two patients, although they were qualified for the targeted deep sequencing. The frequencies of major gene mutations responsible for PDACs were KRAS 90%, CDKN2A 31%, TP53 77%, and SMAD4 29%. A somatic point mutation of NF1, copy number alteration of SMAD4, and loss-of-function of CDKN2A were significantly associated genetic factors for overall survival. Moreover, BRCA2 point mutation was related to liver metastasis. Finally, a clinico-genomic model was developed to estimate the prognosis of patients with PDAC based on clinical parameters and genetic alterations affecting survival in patients; 20 single nucleotide variants and three copy number variations were selected. Targeted deep sequencing on minimal specimens of PDACs was performed, and it was applied to establish a clinico-genomic model for prognosis prediction.

Is endoscopic resection an alternative to surgery for early low-risk submucosal gastric cancers: analysis of a large surgical database.

BACKGROUND: Although endoscopic resection (ER) for early gastric cancers (EGCs) has become popular with the development of endoscopic instruments and skillful endoscopists, the risk of lymph node metastasis (LNM) is still an obstacle in performing ER. In this study, we aimed to identify the risk factors of LNM and validated the expanded criteria, with the goal of suggesting modified criteria for ER in submucosal EGCs. METHODS: Of patients who underwent gastrectomy with LN dissection and were diagnosed as EGCs with depth of invasion such as sm1, sm2 or ≤ 500 µm from 1999 to 2008, 318 EGCs with submucosal invasion ≤ 500 µm were enrolled through pathologic evaluations. To identify the risk factors of LNM, a multivariate analysis of clinicopathologic factors was performed. By combining the independent risk factors of LNM, the risk of LNM was analyzed. RESULT: LNM were detected in 35 cases (11.0 %). Tumors >30 mm in size and with lymphatic invasion were identified as an independent risk factor for LNM in EGCs with depth of invasion ≤ 500 µm. Among 94 cases meeting the expanded criteria, two cases (2.1 %) were found to have LNM. Based on the submucosal invasion <300 µm, there was no LNM in EGCs with a size ≤ 30 mm and no lymphovascular invasion, regardless of differentiation grade. CONCLUSION: To exclude the possibility of LNM, applying the modified criteria based on the submucosal invasion <300 µm in performing ER might be worthwhile.

How to interpret the bile culture results of patients with biliary tract infections.

BACKGROUND/GOALS: Bile is normally sterile, but the presence of organisms in the bile does not necessarily imply an active infection. We wonder what the significance of bile culture results on antibiotics choice in cholangitis with negative blood culture. The aim of this study was to compare organisms cultured from bile with those from blood in bacteremic biliary tract infection and to evaluate factors associated with concordance between blood and bile isolates. METHODS: Between 2000 and 2010, 266 positive blood cultures with concomitant bile culture in bacteremic biliary tract infection were identified. Follow-up bile specimens obtained after negative conversion of blood culture and clinical recovery from acute infection were collected for supplementary analysis. RESULTS: Of the 266 events, 258 showed positive bile culture. Of the 258 bile samples, 80 yielded the same organisms with blood, 129 showed partial agreement and 49 yielded completely different organisms with blood. Only the number of organism was found to be independently associated with concordance. Of the 529 organisms isolated from bile, 227 were found in blood and gram-negative organisms showed higher rate of coincidence than gram-positive organisms. Of the 84 follow-up bile sample, 94% showed persistent positive culture and higher rate of antibiotics resistance than initial bile culture. CONCLUSIONS: More than half of the organisms isolated from bile, especially gram-positive organisms, are not likely to be true pathogens. But single organism cultured from bile has clinical significance. Routine follow-up bile culture in patients showing clinical improvement is not necessary.

Risk factors and a predictive model for acute hepatic failure after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Acute hepatic failure (AHF) is one of the most serious complications of transcatheter arterial chemoembolization (TACE). The aims of this study were to investigate risk factors of AHF after TACE and to establish a predictive model for AHF. METHODS: In the evaluation set, a total of 820 patients who underwent TACE as a first treatment for hepatocellular carcinoma were included. The demographic, laboratory, radiological and treatment-related factors were analysed to identify risk factors for AHF after TACE and a predictive model was established using the identified risk factors. In the validation set, a different cohort of 438 patients was included to validate the predictive model. RESULTS: The incidence of post-TACE AHF was 15.1% (124/820). Multivariate analysis revealed that presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and log alpha-foetoprotein levels, and low albumin and sodium levels were independent risk factors. A mathematical model was established using these independent risk factors, and the area under the receiver operating characteristic curve of the model was 0.773 (95% confidence interval, 0.726-0.820). The cut-off value of 9 had a sensitivity of 78.2%, a specificity of 72.3%, a positive likelihood ratio of 2.82, a negative likelihood ratio of 0.30, a positive predictive value of 28.9% and a negative predictive value of 95.8%. CONCLUSIONS: The risk factors of post-TACE AHF were presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and alpha-foetoprotein levels, and low serum albumin and sodium levels. A mathematical model to predict post-TACE AHF was established.

Clinical impact of inappropriate initial antimicrobial therapy on outcome in bacteremic biliary tract infections.

BACKGROUND: The marked increase in the incidence of biliary tract infections due to antimicrobial-resistant pathogens in recent years is of great concern, as patients infected by these isolates might initially receive antibiotics ineffective against the responsible pathogens. METHODS: A retrospective cohort study including 556 episodes of bacteremic biliary tract infection was designed to evaluate the impact of inappropriate initial antimicrobial therapy on the clinical outcomes of patients with biliary tract infections. RESULTS: Of 556 episodes, 257 (46.2%) received inappropriate initial antimicrobial therapy. Although Escherichia coli and Klebsiella species are the most common pathogens, the pathogens that were most frequently associated with inappropriate therapy were Pseudomonas aeruginosa and Enterococcus spp. In multivariable analysis, inappropriate initial antimicrobial therapy was found to be independently associated with increased mortality (odds ratio (OR) 2.25, 95% confidence interval (CI) 1.13-4.48; p = 0.021), along with pancreaticobiliary tract cancer, liver cirrhosis, Enterobacter infection, and a high Pitt bacteremia score (All p < 0.05). Subgroup multivariate analyses showed that inappropriate initial therapy was not a significant factor associated with mortality in cases where therapeutic decompression or drainage procedures were employed (OR 1.24, 95% CI 0.43-3.54; p = 0.691) or in cases with appropriate definitive antimicrobial therapy (OR 1.61, 95% CI 0.69-3.72; p = 0.270) after adjustment for other variables. CONCLUSIONS: Our findings suggest that the administration of inappropriate initial antimicrobial therapy might be associated with an adverse outcome in patients experiencing bacteremic biliary tract infections, and that the impact of inappropriate therapy on the outcome may be dependent on therapeutic drainage and appropriate definitive antimicrobial therapy.

A case of nonalcoholic steatohepatitis and small intestinal bacterial overgrowth with peripheral edema caused by intestinal bypass surgery and relieved by repair.

Intestinal bypass surgery, particularly jejuno-ileal bypass surgery, performed for the purpose of weight reduction may cause an unexpected exacerbation of nonalcoholic steatohepatitis (NASH). Here, we report a case of NASH caused by small intestinal bacterial overgrowth, which developed after jejuno-colic bypass surgery and resolved dramatically after surgical correction.

The clinical epidemiology and outcomes of bacteremic biliary tract infections caused by antimicrobial-resistant pathogens.

OBJECTIVES: The prevalence of antibiotic-resistant pathogens continues to increase steadily. The aim of this study was to analyze the changing patterns and risk factors of antibiotic resistance in patients with bacteremic biliary tract infections (BTIs). In addition, prognostic factors related to survival in patients with a bacteremic BTI were evaluated. METHODS: Five hundred fifty-six biliary bacteremic events in 411 patients, treated from January 2000 to April 2010, were retrospectively analyzed. In addition, biliary bacteremic events were divided into nosocomial infections (N=396) and community-acquired infections (N=160). RESULTS: The resistance rate to third-generation cephalosporin was higher in 2005-2009 (35 out of 140, 25%, vs. 72 out of 151, 47.7%). The prevalence of extended-spectrum ß-lactamase-producing organisms of Escherichia coli and Klebsiella strains increased markedly from 2.3% (2 out of 86) in 2000-2004 to 43.9% (58 out of 132) in 2005-2009. Nosocomial infection, hospital days before bacteremia, previous hospitalization within 90 days, previous use of antibiotics within 90 days, and an indwelling biliary drainage catheter were found to be independently associated with antibiotic resistance. However, no association was found between antibiotic resistance and mortality in patients with biliary bacteremia. CONCLUSIONS: Antibiotic resistance in bacteremic BTI has increased markedly during the past 10 years. Almost half of nosocomial bacteremic BTI caused by common Gram-negative pathogens during 2005-2009 (58.5%) could not be treated with third-generation cephalosporin. Clinical outcomes were found to be associated with bacteremia severity and underlying illness rather than antibiotic resistance.

A Case of Novel Influenza A (H1N1) Virus Pneumonia Complicated Pnemomediastinum and Subcutenous Emphysema / 결핵및호흡기질환

Recently, a novel influenza A (H1N1) has been recognized as the cause of a worldwide respiratory infection outbreak. Although the symptoms of a novel influenza A (H1N1) are usually mild, the disease can cause severe illness and death. A complication of novel influenza A (H1N1) is pneumomediastinum, a rarely reported condition. We report a case of influenza A (H1N1) complicating pneumomediastinum with subcutaneous emphysema, which had initially presented with blood tinged sputum and chest pain. In addition, we demonstrate bronchoalveolar lavage in influenza A (H1N1).