Objective To assess the feasibility, indications and therapeutic effect of repeatgamma knife radiosurgery for treatment of primary trigeminai neuralgia. Methods From January 1995to February 2006, 277 patients with primary trigeminal neuralgia underwent stereotactic radiosurgerytargeting the cistemal trigeminal nerve with a maximal central dose of 70-80 Gy. A second gamma kniferadiosurgery with a maximal central dose of 65-80 Gy was performed in 23 patients with refractory and15 with recurrent trigeminal neuralgia after the primary surgery. The 50% isodose line encompassed thetarget area for radiation. The trigeminal root entry zone was included in a single target area in 33 patients,and in 5 patients, two target areas were chosen. Results All patients were followed up for 12 to 108months (mean 55 months) by telephone. The pain relief lasted for 1 to 180 days (mean 120 days) after thesecond gamma knife radiosurgery. The primary stereotactic radiosurgery resulted in a complete or partialpain relief rate of 91.7%(254/277). In the 23 patients with refractory trigeminal neuralgia, the secondradiosurgery achieved a pain relief rate of 73.9% (17/23), significantly lower than the rate of 100%(15/15) in the 15 patients with recurrent trigeminal neuralgia (P=0.045). Facial numbness or paresthesiaoccurred in 30 patients (10.8%) after the primary radiosurgery, and in another 8 patients (21.1%) after thesecond surgery. Conclusion Gamma knife stereotactic radiosurgery is safe and effective and causesfew complications for relieving trigeminal neuralgia. A repeat gamma knife stereotactic radiosurgery isalso effective for management of recurrent or refractory trigeminal neuralgia, especially in recurrentcases.

OBJECTIVETo characterize oncogenic KIT signaling mechanisms in gastrointestinal stromal tumor(GIST), and to determine which signaling pathway might be of potential relevance to imatinib acquired resistance.

METHODSThe mutations of KIT and PDGFRa gene were evaluated and KIT downstream signaling profiles were evaluated in 8 specimen from 5 GIST patients who were evaluated treated between 2003 and 2008 in our hospital. Biochemical inhibition of the expression of related proteins in Ras/Raf/MAPK and PI3-K/AKT pathways, such as KIT, mitogen-activated protein kinase(MAPK),mammalian target of rapamycin(MTOR), AKT, Proliferating cell nuclear antigen (PCNA) and BCL-2, were determined by Western blotting for protein activation.

RESULTSThree cases who showed response to imatinib carried primary mutations in KIT gene, with 2 cases possessing mutation in exon 11, 1 case in exon 13. One case with imatinib-resistance developed KIT secondary mutation, but all the cases had no PDGFRa mutation. p-KIT and p-AKT expressions were higher in the samples of imatinib-resistant GIST than those of imatinib-responsive GIST. Total KIT, MAPK, p-MAPK, p-MTOR expressions were strong and comparable in all varied GISTs, which had no significant difference between imatinib-resistant and imatinib-responsive samples. PCNA and BCL-2 expression varied in samples of different therapy cycles and different location.

CONCLUSIONSRas/Raf/MAPK and PI3-K/AKT/MTOR pathways are essential to GIST pathogenesis. The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST.

Benzamides ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; Mutation ; Piperazines ; pharmacology ; Proto-Oncogene Proteins c-kit ; genetics ; Pyrimidines ; pharmacology ; Signal Transduction ; drug effects ; genetics

OBJECTIVETo explore the role of surgery and its long-term outcome in patients with advanced gastrointestinal stromal tumor(GIST) treated with imatinib preoperatively.

METHODSThirteen patients receiving imatinib therapy preoperatively, were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection.

RESULTSThirteen patients, including 3 patients with locally advanced primary GIST and 10 patients with recurrent or metastatic GIST, underwent surgery after preoperative treatment with imatinib. Complete resections were accomplished in 4 of the 5 responsive disease(RD) patients, and in 1 of the 8 progression disease(PD) patients (38.5%). The progression-free survival(PFS) time for patients with RD and PD were 24.8 months and 2.8 months respectively. The difference of PFS between patients with RD and those with PD was significant(P<0.01). Median overall survival(OS) was not reached in both patients with RD and PD. The difference of OS between patients with RD and those with PD was not significant(P>0.05).

CONCLUSIONSurgical intervention following imatinib is feasible and can be considered for patients with advanced GIST responsive to imatinib.

Antineoplastic Agents ; administration & dosage ; Benzamides ; Disease-Free Survival ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Piperazines ; administration & dosage ; Prognosis ; Pyrimidines ; administration & dosage ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the status of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors (GIST) and explore the relationship between the mutations and the clinical features.

METHODSOne hundred and forty-one cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9,11,13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing. The relations of clinical features and mutational status were analyzed with statistical tools in this study.

RESULTSAmong the 141 GISTs, c-kit mutations were identified in 76.6% (108/141): 70.2% (99/141) involving exon 11, 5.7% (8/141) involving exon 9, 0.7% (1/141) involving exon 13 and no mutation detected in exon 17. The gene mutations were mostly heterogeneous. The c-kit exon 11 mutational format included deletion (65.7%), point mutation (24.2%) and insert duplications(10.1%).The mutations clustered in the classic "hot spot" at the 5' end of the exon mostly heterogeneous and the second "hot spot" were internal tandem duplications (ITD) at the 3' end of the exon. PDGFRA mutations were totally identified in 12.1%(4/33) of no-c-kit-mutation GISTs and 40%(4/10) of CD117-negative GISTs: all involving exon 18 with the mutations D842V. With the analysis between clinical features and mutation status, the significant difference of gene mutation rate in the different primary tumor organs (chi(2)=7.229, P=0.027, chi(2)=7.000,P=0.03) and no significant differences between the groups of age,gender,tumor size,mitotic rate,grade of malignant potential were found.

CONCLUSIONMost GISTs have the c-kit or PDGFRA gene mutation. There are significant difference between mutation and primary tumor organ.

Adult ; Aged ; Exons ; Female ; Gastrointestinal Stromal Tumors ; genetics ; pathology ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Proto-Oncogene Proteins c-kit ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics

BACKGROUNDAcute kidney injury (AKI) has been recognized as a major healthcare problem affecting millions of patients worldwide. However, epidemiologic data concerning AKI in China are still lacking. The objectives of this study were to characterize AKI defined by RIFLE criteria, assess the association with hospital mortality, and evaluate the impact of AKI in the context of other risk factors.

METHODSThis prospective multicenter observational study enrolled 3,063 consecutive patients from 1 July 2009 to 31 August 2009 in 22 ICUs across mainland China. We excluded patients who were admitted for less than 24 hours (n = 1623), younger than 18 years (n = 127), receiving chronic hemodialysis (n = 29), receiving renal transplantation (n = 1) and unknown reasons (n = 28). There were 1255 patients in the final analysis. AKI was diagnosed and classified according to RIFLE criteria.

RESULTSThere were 396 patients (31.6%) who had AKI, with RIFLE maximum class R, I, and F in 126 (10.0%), 91 (7.3%), and 179 (14.3%) patients, respectively. Renal function deteriorated in 206 patients (16.4%). In comparison with non AKI patients, patients in the risk class on ICU admission were more likely to progress to the injury class (odds ratio (OR) 3.564, 95% confidence interval (CI) 1.706 - 7.443, P = 0.001], while patients in the risk class (OR 5.215, 95% CI 2.798-9.719, P < 0.001) and injury class (OR 13.316, 95% CI 7.507-23.622, P < 0.001) had a significantly higher probability of deteriorating into failure class. The adjusted hazard ratios for 90-day mortality were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the failure group.

CONCLUSIONSThe prevalence of AKI was high among critically ill patients in Chinese ICUs. In comparison with non-AKI patients, patients with RIFLE class R or class I on ICU admission were more susceptibility to progression to class I or class F. The RIFLE criteria were robust and correlated well with clinical deterioration and mortality.

Acute Kidney Injury ; epidemiology ; etiology ; pathology ; Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Middle Aged ; Prospective Studies ; Risk Factors

BACKGROUNDUrine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr).

METHODSWe conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses.

RESULTSThe prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality.

CONCLUSIONUO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.

Acute Disease ; mortality ; Aged ; Creatinine ; blood ; Critical Illness ; mortality ; Female ; Hospital Mortality ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases ; blood ; mortality ; pathology ; urine ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors