Influence of Chromosome Abnormality on Therapeutic Efficacy and Prognosis of Newly Diagnosed Multiple Myeloma Treated with Bortezomib / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the influence of chromosome abnormality on therapeutic efficacy and prognosis of patients with newly diagnosed multiple myeloma(MM) treated with bortezomib.</p><p><b>METHODS</b>The clinical data of 152 patients with newly diagnosed MM were collected from January 2008 to December 2011. All patients received bortezo-mib-based chemotherapy and the therapeutic efficacy were investigated for 4 cycles later. The R banding and DNA probe were used to analyze the chromosome and gene (RB1 deletion, D13S319 deletion, P53 deletion, IgH rearrangement and 1q21 amplification) of chromosome specimens. Moreover, the therapeutic efficacy and long-term survival data were analyzed among the patients with different types of chromosomal abnormality. The Kaplan-Meier was applied to analyze survival, and COX risk proportional model was used for multivariate analysis.</p><p><b>RESULTS</b>Among 152 patients with MM, there were 47 cases(30.92%) of abnormal karyotype, 43 cases(28.29%) of abnormal RB1,49 cases (32.24%) of abnormal D13S319, 30 cases (19.74%) of abnormal P53, 58 cases (38.16%) of abnormal IgH and 33 cases (21.71%) of abnormal chromosome 1q21. All the patients were evaluable for the therapeutic efficacy, including 24 CR, 54 nCR, 21 PR, 14 MR and 39 PD with response rate of 74.34% and remission rate of 50.66%. Compared with normal controls, the response and remission rate were lower than that in the patients with abnormal karyotype of D13S319, P53 or IgH, and remission rate was lower in the patients with RB1 or 1q21 (P<0.05). All the patients were followd-up (median: 52.0 months, range: 22-72 months), but median overall survival(OS) was not yet reached at the end of the follow-up. The median OS was in the patients with different chromosome versus the normal subjects (P<0.05). The chromosome abnormality was found to affect the prognosis of MM by COX multivariate analysis. In regard to the normal subjects, the risk for poor prognosis increased by 1.177, 2.639, 6.552, 3.124, 2.045 and 7.264 fold in the patients with abnormal Karyotype of RB1, D13S319, P53, IgH and 1q21, respectively.</p><p><b>CONCLUSION</b>The abnormality of chromosome can influence the efficacy and prognosis of newly diagnosed MM patients treated with bortezomib. The detection of chromosomal abnormalities has a certain reference value for the treatment of primary MM.</p>

Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET.</p><p><b>METHODS</b>We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features.</p><p><b>RESULTS</b>CALR, JAK2V617F, and MPLW515 mutations were detected in 30% (n = 92), 48% (n = 149), and 1% (n = 4) of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 (52-bp deletion) and Type 2 (5-bp insertion, TTGTC) mutations, leading to del367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell (WBC) count, and higher platelet count compared to those with mutated JAK2 (P < 0.05). Furthermore, a significant difference was found in WBCs between wild-type patients (triple negative for JAK2, MPL, and CALR mutations) and patients with JAK2 mutations. Patients with CALR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET (P < 0.05).</p><p><b>CONCLUSIONS</b>CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared with JAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, CALR is a potentially valuable diagnostic marker and therapeutic target in ET.</p>

Value of abdominal ultrasound scan, CT and MRI for diagnosing inferior vena cava tumour thrombus in renal cell carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>We used abdominal ultrasound scan (USS), computed tomography (CT) and magnetic resonance imaging (MRI) findings in venous spread of renal cell carcinoma (RCC) to determine the superior extent of inferior vena cava (IVC) thrombus and IVC wall invasion and compared them with surgical and pathological reports.</p><p><b>METHODS</b>From January 1999 to August 2007, 25 patients were diagnosed with RCC with IVC tumour thrombus. Before their operation, all patients had USS, contrast enhanced CT and MRI to find the superior extent of tumour thrombus and IVC wall invasion. All postprocessing techniques were performed by experienced radiologists. Two pathologists reported on all pathology specimens. The superior extent of tumour thrombus was confirmed by the senior surgeon at each operation, using the levels of thrombus defined according to 2004 Mayo Clinic classification. The radiographic results were compared with surgical and pathological findings.</p><p><b>RESULTS</b>All patients had radical nephrectomy and tumour thrombus excision. Eight patients had RCC on the left side and 17 on the right side. According to the clinical and pathological findings, 6 patients had level I tumour thrombus, 9 level II, 5 level III and 5 level IV. Six patients had IVC wall invasion. No patient had evidence of lymph node or distant metastases. Of the 25 patients, USS correctly diagnosed the superior extent of tumour thrombus in 18/25, CT 23/25 and MRI 23/25. USS found 1 case of IVC wall invasion preoperatively.</p><p><b>CONCLUSIONS</b>Multidetector computed tomography and magnetic resonance imaging are comparable and more effective than abdominal ultrasound in diagnosing inferior vena cava tumour thrombus in renal cell carcinoma. None of the three methods can detect inferior vena cava wall invasion.</p>

Urodynamic analysis of dysuria in female patients / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the urodynamic diagnostic types of dysuria in female patients of different age groups.</p><p><b>METHODS</b>Six hundred and sixteen female patients with dysuria were evaluated from March 1997 to July 2008. No patients had history of nervous system disease and history of lower urinary tract operations. They had detrusor pressure-flow studies and uroflowmetry. The urodynamic diagnostic types were analyzed in 3 different age groups.</p><p><b>RESULTS</b>In 3 groups of 18 - 40 years, 40 - 60 years and > or = 60 years, the diagnosis of bladder outlet obstruction (BOO) had the highest proportion (54.8%, 59.1% and 45.0% respectively). The distribution of detrusor overactivity, detrusor under-activity and normal function had no significant difference between 3 groups. The distribution of BOO and acontractile detrusor had significantly difference between 3 groups. When groups of 18 - 40 years and 40 - 60 years were combined into 18 - 60 years group and compared with the older group, the proportion of BOO, acontractile detrusor and detrusor under-activity showed significantly difference. The proportions of BOO in the two groups were 57.3% and 45.0%, acontractile detrusor 15.6% and 23.9%, detrusor under-activity 17.4% and 25.0%, respectively. The proportion of reduced bladder sensation among detrusor under-activity patients in the older group was significantly higher.</p><p><b>CONCLUSIONS</b>In the urodynamic diagnoses of voiding difficulty in female patients, bladder outlet obstruction has the highest proportion. This proportion decreases in the older patients. The proportion of acontractile detrusor and detrusor under-activity increases in the older group.</p>

Analysis of biallelic inactivation of the von Hippel-Lindau tumor suppressor gene VHL in patients of renal cell carcinoma patient / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) in patient of renal cell carcinoma (RCC) patient.</p><p><b>METHODS</b>We extracted tumor and normal DNA from 41 RCC patients. Mutation of VHL gene from tumor tissue was detected from tumor tissue by polymerase chain reaction (PCR) and direct sequencing. Two single nucleotide polymorphism (SNP) sites located in VHL gene were analyzed by PCR restriction fragment length polymorphism, and loss of heterozygosity (LOH) was analyzed for VHL gene by comparing between tumor with normal tissue.</p><p><b>RESULTS</b>Mutation and LOH of VHL gene was found in 51% (21/41) and 42% (8/19) of RCC patients respectively. LOH was highly associated with mutation positive tumors (r = 0.78) and VHL biallelic inactivation was detected in 37% of RCC patients.</p><p><b>CONCLUSION</b>Biallelic inactivation of VHL gene occurs in RCC due to VHL mutation and LOH, and its frequency rate is 37%.</p>

Somatic mutations of VHL gene and HIF-1alpha expression in primary renal clear cell carcinomas / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the significance of somatic mutations of VHL gene and hypoxia-inducible factor-1alpha (HIF-1alpha) expression in primary renal clear cell carcinoma (RCC).</p><p><b>METHODS</b>Mutation of VHL gene and HIF-1alpha expression were detected by means of PCR, denaturing high-performance liquid chromatography (DHPLC), direct sequencing and immunohistochemistry in 32 samples from primary renal clear cell carcinoma patients.</p><p><b>RESULTS</b>In 32 RCC samples, 17 samples (53.1%) had and 32 samples of adjacent nonmalignant renal tissue had not mutations of VHL gene expression. Twelve RCC samples (70.6%) which had mutations of VHL gene expressed HIF-1alpha, and it had significant difference to 4 RCC (26.7%) samples which didn't have mutations of VHL gene (P < 0.05).</p><p><b>CONCLUSION</b>Mutations of VHL gene may play a significant role in the tumorigenesis of RCC, and HIF-1alpha expression correlates with it.</p>