Objective To screen for molecular markers associated with the prognosis of extrahepatic cholangiocarcinoma (EHCC) after radical excision by observing the difference of bile metabolomics during perioperative period. Methods Twenty-seven patients with EHCC, including 19 with hilar cholangiocarcinoma and 8 with distal cholangiocarcinoma, were included in this study. Their bile samples were collected before and 1, 7 days after operation. Metabonomics method using gas chromatograph^mass spectrometry (GC-MS) was employed to analyze the different metabolites at different time points. Correlation analysis was performed between the common different metabolites and the patient prognosis. Results Five kinds of metabolites in the bile were notably increased 1 day after operation compared with that before operation, no metabolites were decreased. Three kinds of metabolites were notably increased and another 3 were notably decreased 7 days after operation compared with before operation. Among the above two groups of different metabolites, there were 2 common metabolites: benzoic acid and methylmalonic acid. The one year recurrence rate of patients with benzoic acid increased ≥2 times at 7 days after operation was significantly lower than that increased <2 times (P= 0. 04). No significant correlation was found between the change of methylmalonic acid and the early relapse in 1 year after operation. Moreover, bivariate correlation showed that the changes of benzoic acid metaboilic level in bile were not significantly correlated with the serum CA19-9, age of patients, or TNM stage (P>0. 05). Conclusion The change of benzoic acid metaboilic level in bile during perioperative period can help to predict the early relapse in extrahepatic cholangiocarcinoma patients after curative resection.

This study was aimed to investigate the correlation of NPM1 and FLT3-ITD mutations with leukocyte count in peripheral blood and bone marrow blasts in patients with acute myeloid leukemia (AML). Fifty-one acute myeloid leukemia patients with normal karyotype from January 2009 to December 2011 were enrolled in this study. The clinical data of 51 cases were analyzed retrospectively. Out of 52 cases 22 were male, and 29 were female. The median age was 47 years old (ranged from 14 to 83 years old). The de novo patients were examined by bone marrow cytomorphology and blood routine analysis. Polymerase chain reaction was used to analyze the NPM1 and FLT3-ITD mutations. The results showed that the patients with NPM1 mutations had higher leukocyte count compared with those without mutations (30.7×10(9)/L vs 8.6×10(9)/L, P = 0.002). FLT3-ITD mutation was related to higher leukocyte count (42.38×10(9)/L vs 11.45×10(9)/L without mutation, P = 0.033) and blasts (74.0% vs 60.25% without mutation, P = 0.036). The leukocyte count and percentage of bone marrow blasts were lowest in the patients with neither mutations, and gradually increasing in the NPM1(-) mutation, FLT3-ITD(-) mutation, and NPM1(+) mutation, FLT3-ITDI(+) mutation, and NPM1(+)/FLT3-ITD(+) mutation groups (P < 0.05). The patients tended to have NPM1 (P = 0.002) and FLT3-ITD (P = 0.033) mutations when their leukocyte counts were more than 12.55×10(9)/L and 37.85×10(9)/L, respectively. Those with bone marrow blast more than 72.25% showed higher rate of FLT3-ITD mutation (P = 0.008). Patients with NPM1 mutations had higher complete remission rate than those without NPM1 mutation (78.13% vs 40.0%, χ(2) = 4.651, P = 0.031) after remission induction therapy. It is concluded that both NPM1 and FLT3-ITD mutations are linked to higher leukocyte count and blast percentage, suggesting that both mutations may be associated with increased proliferation of leukemia cells, and may have a synergistic function in stimulating proliferation.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Karyotype ; Karyotyping ; Leukemia, Myeloid, Acute ; blood ; genetics ; Leukocyte Count ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo analyze the cytogenetic characteristics of different age subgroups in patients with acute myeloid leukemia (AML), and to explore the relationship between age and cytogenetics.

METHODSBetween January 2004 and December 2011, Bone marrow (BM) samples from 640 patients with de novo AML were analyzed retrospectively. The analyses were performed according to standard culturing and banding techniques, and clonal abnormalities were defined and described according to the International System for Human Cytogenetic Nomenclature (ISCN 2009). The cytogenetic subtypes were performed as normal, balanced, and unbalanced karyotypes. In the last group, the age distribution of complex and monosome karyotypes were further analyzed. The patients were divided into 8 age groups: 0 - 9, 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, 60 - 69, and ≥ 70 year old groups.

RESULTSThe distribution of normal, balanced, and unbalanced karyotypes showed age specific characteristics. The incidence of normal karyotype increased from 6.67% (0 ∼ 9 year old) to 58.33% (≥ 70) (χ(2) = 20.68, P = 0.001) and balanced karyotype decreased from 73.33% (0 ∼ 9) to 11.11% (≥ 70) (χ(2) = 48.22, P < 0.01). The frequency of unbalanced karyotypes increased from 20.0% (0 ∼ 9) to 30.56% (≥ 70) (χ(2) = 18.963, P = 0.008). The frequency of complex karyotype was 6.67% in 0 - 9 year old group, followed by 0% in 10 - 19 and 20 - 29 year old group, and from 1.72% to 11.11% from 30 - 39 to ≥ 70 year old group (χ(2) = 8.341, P = 0.08). Monosome karyotype was only detected in patients in 30 year old or older groups. Although an increased tendency was observed with ages, there was no significant difference (χ(2) = 4.778, P = 0.311).

CONCLUSIONThe different age profiles of the cytogenetic subtypes may indicate the different mechanisms of the pathogenesis of AML, which may also offer beneficial information for etiological research of AML.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Karyotype ; Karyotyping ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Retrospective Studies ; Young Adult