Influence of pulling direction on knot security: A laboratory research.

BACKGROUND: When tying knots, some surgeons do not pay particular attention to the direction in which they pull to lay down throws. We examine to what extent does pulling direction influence on knot security. METHODS: A total of 368 residents were instructed to tie knots with from 2 to 7 throws using silk braided suture in 3-0 gauge. The direction in which they pulled to lay down throws was recorded. Only the knots tied either by pulling in alternate directions (Group A) or in constant direction (Group C) from the first throw to the last were involved in statistical analysis. Tensile strength and untying rate of the knots were then measured for comparative analysis. RESULTS: For knots with from 2 to 7 throws, the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively. For knots with from 5 to 7 throws, the untying rate of the ones from Group A was significantly lower than that of the ones from Group C (p < 0.05), respectively. For the unraveled knots with from 2 to 7 throws (except for the ones with 5 throws), the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively. CONCLUSION: Pulling in constant direction results in inferior knot security. Surgeons must ascertain the influence of pulling direction on knot security, and try to achieve superior security with fewer throws to ensure patient safety.

The prognostic value of the controlling nutritional status score in patients with myelodysplastic syndrome.

PURPOSE: To evaluate the prognostic value of the controlling nutritional status score (CONUT) in patients with myelodysplastic syndrome (MDS). METHODS: The clinical data of 81 newly diagnosed MDS patients treated with decitabine in the hematology ward of our hospital from October 2009 to September 2020 were analyzed retrospectively. According to the ROC curve of overall survival (OS), the best cutoff value of CONUT was obtained. MDS patients were divided into high CONUT score group and low CONUT score group according to the best cut-off value, and their clinical characteristics and survival were analyzed. RESULTS: Among the 81 patients with MDS, there were 32 cases in the high CONUT score group and 49 cases in low CONUT score group. Compared with the low CONUT group, the high CONUT group had lower levels of hemoglobin, lymphocyte count, albumin, and total cholesterol (P = 0.037, < 0.001, 0.009, < 0.001). The median OS of low and high CONUT groups were 17.2 and 11.0 months (P = 0.017). According to the results of univariate and multivariate survival analysis of OS, thrombocytopenia, high CONUT score, and medium and high risk IPSS-R score were independent prognostic factors. CONCLUSION: High CONUT score is associated with low hemoglobin in patients with MDS. High CONUT score indicates poor OS and it is an independent prognostic factor in patients with MDS.

Association of CD117 and HLA-DR expression with shorter overall survival and/or progression-free survival in patients with multiple myeloma treated with bortezomib and thalidomide combination treatment without transplantation.

Certain immunophenotypes in multiple myeloma (MM), including CD56 and CD117, have been reported to be associated with overall survival (OS). However, previous reports have ignored the impact of different treatment regimens and the long-term prognostic value of immunophenotyping in MM when treated with novel agents, including thalidomide and bortezomib, in the absence of transplantation for autologous stem cell transplantation and allo-hematopoietic stem cell transplantation. To further understand the long-term prognostic value of immunophenotyping in MM, when treated with bortezomib combined with thalidomide-based regimens without transplantation, 80 patients who were newly diagnosed between January 2007 and December 2015, were analyzed retrospectively. In contrast to previous studies, no significant survival time difference was observed between CD56+/CD117+ and CD56-/CD117- groups. Multivariate analysis suggested that human leukocyte antigen-antigen D-related (HLA-DR)+ was independently associated with shorter OS and progression-free survival (PFS), while CD117+ was an independent prognostic factor for decreased PFS. In addition, the myeloma prognostic index (MPI), defined by HLA-DR+, age ≥65 years and international staging system stage III, was suitable for risk stratification of patients treated with novel agents for OS and PFS. The results of the current study suggested that HLA-DR+ patients had a shorter OS and PFS and CD117+ patients had shorter PFS. HLA-DR+ or CD117+ was sufficient to affect survival. Evaluating these markers may reveal valuable prognostic factors for MM in patients receiving bortezomib combined with thalidomide-based regimens without autologous stem cell transplantation and allo-hematopoietic stem cell transplantation). MPI may describe an accessible tool to predict the prognosis of patients with MM.

Limited Prognostic Value of Pretreatment Neutrophil-to-Lymphocyte Ratios in Elderly Patients with Multiple Myeloma.

BACKGROUND: Recent studies reported neutrophil to lymphocyte ratio (NLR) as a predictor of overall survival (OS) in multiple myeloma (MM). However, the role of NLR at diagnosis in elderly patients with MM has been less explored. Therefore, we aimed to investigate the relationships between NLR and prognosis in elderly patients with MM. METHODS: We retrospectively analyzed the data for 76 newly diagnosed elderly MM patients between January 1, 2007 and September 31, 2015. Seventy-six age- and gender-matched healthy controls were also included in the study. RESULTS: NLR was significantly higher in MM patients than the control group (2.9 ± 2.29 vs. 1.88 ± 0.54, respectively; p < 0.0001). Patients with a NLR < 2 at diagnosis had slightly better OS when compared to those with a NLR ≥ 2 (41 and 36 months, respectively), but the differences were not statistically significant. The elevated NLR did not predict response to initial therapy. Patients were regrouped into the bortezomib group and the non-bortezomib group. In the bortezomib group, notably the OS was borderline significantly longer in the patients with NLR < 2 when compared to those with NLR ≥ 2 (48 months vs. 25 months, p = 0.041). In the multivariate analysis, ISS III stage and high lactate dehydrogenase levels were significantly associated with OS. CONCLUSIONS: We found NLR had no effect on prognosis in newly diagnosed elderly MM patients. Further studies focused on this subject are warranted.

[Influence of Chromosome Abnormality on Therapeutic Efficacy and Prognosis of Newly Diagnosed Multiple Myeloma Treated with Bortezomib].

OBJECTIVE: To explore the influence of chromosome abnormality on therapeutic efficacy and prognosis of patients with newly diagnosed multiple myeloma(MM) treated with bortezomib. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A simply prepared small-diameter artificial blood vessel that promotes in situ endothelialization.

Synthetic grafts are of limited use in small-diameter vessels (Φ<6mm) due to the poor patency rate. The inability of such grafts to achieve early endothelialization together with the compliance mismatch between the grafts and the native vessels promote thrombosis, which eventually leads to graft occlusion. In the current study, stromal cell-derived factor (SDF)-1α/vascular endothelial growth factor (VEGF)-loaded polyurethane (PU) conduits were simply prepared via electrospinning. The mechanical property, drug release behavior and cytocompatibility of the conduits were investigated. The effects of the conduits on endothelial progenitor cell (EPC) mobilization and differentiation were examined in vitro. Then, the conduits were implanted as canine femoral artery interposition grafts. The results revealed that SDF-1α and VEGF were quickly released shortly after implantation, and the conduits exhibited slow and sustained release thereafter. The cytokines had definite effects on EPC mobilization and differentiation in vitro and promoted conduit endothelialization in vivo. The conduits had good tissue compatibility and favorable compliance. All of these features inhibited the conduits from being occluded, thereby improving their long-term patency rate. At 6th month postoperatively, 5 of the 8 grafts were patent while all the 8 grafts without the cytokines were occluded. These findings provide a simple and effective method for the construction of small-diameter artificial blood vessels with the aim of facilitating early endothelialization and improving long-term patency. STATEMENT OF SIGNIFICANCE: (1) SDF-1α/VEGF loaded PU conduits were simply prepared by electrospinning. The cytokines with definite and potent effects on angiogenesis were used to avoid complicated mechanism researches. Compared with most of the current vascular grafts which are of poor strength or elasticity, the conduits have favorable mechanical property. All of these inhibit the conduits from occlusion, and thus improve their long-term patency rate. (2) For the in vivo tests, the dogs did not receive any anticoagulant medication in the follow-up period to expose the grafts to the strictest conditions. In vivo endothelialization of the conduits was thoroughly investigated by Sonography, HE staining, SEM and LSCM. The study will be helpful for the construction of small-diameter artificial blood vessels.

Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Evaluation of three-dimensional printing for laparoscopic partial nephrectomy of renal tumors: a preliminary report.

OBJECTIVES: To investigate the impact of three-dimensional (3D) printing on the surgical planning, potential of training and patients' comprehension of minimally invasive surgery for renal tumors. METHODS: Patients of a T1N0M0 single renal tumor and indicated for laparoscopic partial nephrectomy were selected. CT data were sent for post-processing and output to the 3D printer to create kidney models with tumor. By presenting to experienced laparoscopic urologists and patients, respectively, the models' realism, effectiveness for surgical planning and training, and patients' comprehension of disease and procedure were evaluated with plotted questionnaires (10-point rating scales, 1-not at all useful/not at all realistic/poor, 10-very useful/very realistic/excellent). The size of resected tumors was compared with that on the models. RESULTS: Ten kidney models of such patients were fabricated successfully. The overall effectiveness in surgical planning and training (7.8 ± 0.7-8.0 ± 1.1), and realism (6.0 ± 0.6-7.8 ± 1.0) were reached by four invited urologists. Intraoperative correlation was advocated by the two performing urologists. Patients were fascinated with the demonstration of a tactile "diseased organ" (average ≥ 9.0). The size deviation was 3.4 ± 1.3 mm. CONCLUSIONS: Generating kidney models of T1N0M0 tumors with 3D printing are feasible with refinements to be performed. Face and content validity was obtained when those models were presented to experienced urologists for making practical planning and training. Understandings of the disease and procedure from patients were well appreciated with this novel technology.

Rapid evolving into acute myeloid leukemia in a patient with multiple myeloma and concurrent myelodysplasia after VTD therapy.

The association of Myelodysplasia (MDS) and multiple myeloma (MM) has been usually described not only as a complication of chemotherapy but also in the absence of preceding chemotherapy or together at the time of diagnosis. Optimal therapies of a coexisting MM and MDS have not been well established up to now. We report a case of MDS diagnosed simultaneously with MM. After treatment with VTD (bortezomib, thalidomide, dexamethasone) marked anti-myeloma activity was observed, but it was associated with rapid progression of the MDS to acute myeloid leukemia (AML). The leukemic transformation in our case most probably reflects the natural progression of MDS, though it clearly demonstrates that VTD is ineffective in controlling blast proliferation in MDS. To our knowledge, this is the first case report on MDS in the setting of MM with rapid evolution to AML to VTD therapy. More data from more cases are needed, to find the potential utility of VTD therapy in coexisting MDS and MM patients.

Characteristics of urinary tract infection pathogens and their in vitro susceptibility to antimicrobial agents in China: data from a multicenter study.

OBJECTIVE: This study assessed the characteristics of pathogens identified in clinical isolates from patients with urinary tract infection (UTI) and their in vitro sensitivity to commonly used antibiotics in the clinical setting in China. DESIGN AND SETTING: Multicenter study was conducted between January and December 2011 in 12 hospitals in China. PARTICIPANTS: Urine samples were collected from 356 symptomatic patients treated in the study hospitals for acute uncomplicated cystitis, recurrent UTI or complicated UTI. PRIMARY AND SECONDARY OUTCOME MEASURES: Minimal inhibitory concentrations (MICs) were measured using broth microdilution according to the Clinical and Laboratory Standards Institute 2011 guidelines. Thirteen antimicrobial agents were tested: fosfomycin tromethamine, levofloxacin, moxifloxacin, cefdinir, cefixime, cefaclor, cefprozil, cefuroxime, amoxicillin/clavulanic acid, cefotaxime, azithromycin, nitrofurantoin and oxacillin. Escherichia coli isolates were screened and extended spectrum ß-lactamases (ESBL) production was confirmed by a double-disk synergy test. RESULTS: 198 urine samples were culture-positive and 175 isolates were included in the final analysis. E coli was detected in 50% of cultures, followed by Staphylococcus epidermidis (9%), Enterococcus faecalis (9%) and Klebsiella pneumoniae (5%). The detection rate of ESBL-producing E coli was 53%. Resistance to levofloxacin was the most common among all the isolates. Nitrofurantoin and fosfomycin tromethamine had the greatest activity against E coli; overall, 92% and 91% of isolates were susceptible to these antimicrobials. E faecalis had the highest susceptibility rates to fosfomycin tromethamine (100%). CONCLUSIONS: The most frequently identified pathogens in our patients were ESBL-producing E coli and E faecalis. Fosfomycin tromethamine and nitrofurantoin showed a good antimicrobial activity against UTI pathogens. They may represent good options for the empiric treatment of patients with UTI.

Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: an uncontrolled, open-label, multicentre study.

OBJECTIVE: To evaluate the clinical and microbiological efficacy and safety of three doses of 3 g fosfomycin tromethamine administered orally to treat lower urinary tract infections. DESIGN AND PARTICIPANTS: This prospective, uncontrolled, open-label study was conducted in 12 medical centres in China, between January and December 2011. According to the diagnosis criteria of Chinese Guidelines on Urological Infections, patients (18-70 years) with acute uncomplicated cystitis, recurrent lower urinary tract infection or complicated lower urinary tract infection received three doses of 3 g fosfomycin tromethamine orally, at days 1, 3 and 5. PRIMARY AND SECONDARY OUTCOME MEASURES: Efficacy endpoints (clinical efficacy, microbiological efficacy and overall efficacy) were evaluated on day 15. Clinical symptoms, physical signs, urinalysis, liver and kidney function, patient records and evaluation of adverse events (AEs) and serious AEs up to day 15 were evaluated for analysis of safety. RESULTS: 361 patients were included in the full analysis set, 356 in the safety analysis set and 335 in the per-protocol set (PPS). In the PPS, the clinical efficacy rates at day 15 for acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection were 94.71% (179/189), 77.22% (61/79) and 62.69% (42/67), respectively. The microbiological efficacy rates (day 15) were 97.65% (83/85), 94.44% (34/36) and 83.87% (26/31), respectively. The overall efficacy rates (day 15) were 95.29% (81/85), 77.78% (28/36) and 64.52% (20/31), respectively. 20/356 (5.6%) patients reported drug-related AEs, the most common being diarrhoea. No serious drug-related AEs were reported. CONCLUSIONS: This fosfomycin tromethamine dosing regimen showed clinical and microbiological efficacy with some AEs and good tolerability in patients with acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection.

Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma.

AIM: To investigate the frequency and clinical significance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tissue from 49 CRC patients were analyzed. Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation and were subjected to a flow cytometry-based immunophenotypic analysis. RESULTS: A considerable increase in the percentage of CD33⁺HLA-DR⁻ MDSCs was observed in the peripheral blood (1.89% ± 0.75%) and tumor tissues (2.99% ± 1.29%) of CRC patients as compared with that in the peripheral blood of healthy controls (0.54% ± 0.35%). This expanded CD33⁺HLA-DR⁻ subset exhibited immature myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Further studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis(P = 0.023), whereas that in tumor tissues was correlated with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION: Characterization of MDSCs in CRC suggests the clinical significance of circulating and tumor-infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.

Value of abdominal ultrasound scan, CT and MRI for diagnosing inferior vena cava tumour thrombus in renal cell carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Urodynamic analysis of dysuria in female patients].

OBJECTIVE: To compare the urodynamic diagnostic types of dysuria in female patients of different age groups. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Analysis of biallelic inactivation of the von Hippel-Lindau tumor suppressor gene VHL in patients of renal cell carcinoma patient].

OBJECTIVE: To investigate biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) in patient of renal cell carcinoma (RCC) patient. METHODS: 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. RESULTS: 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. CONCLUSION: Biallelic inactivation of VHL gene occurs in RCC due to VHL mutation and LOH, and its frequency rate is 37%.

[Mutation of von Hippel-Lindau gene and expression of vascular endothelial growth factor in sporadic clear cell renal cell carcinoma and their relationships to angiogenesis].

OBJECTIVE: To evaluate the relationship between the mutation of the von Hippel-Lindau (VHL) gene and expression of vascular endothelial growth factor (VEGF) in sporadic clear cell renal cell carcinoma (CCRCC) and angiogenesis. METHODS: Polymerase chain reaction (PCR) was used to detect the mutation of VHL gene in the specimens of cancerous tissue and normal tissues away from tumor from 77 patients with CCRCC. Immunohistochemistry was used to examine the expression of VEGF. CD34 staining was used to measure the microvascular density (MVD). RESULTS: VHL gene mutations were detected in 40 cases (51.9%). The expression rate of VEGF was 79.2% (61 cases). The positive rate of VEGF in the cases with VHL mutation was 92.5%, significantly higher than that in the cases without VHL mutation (64.9%, P = 0.003). The levels of MVD was higher in the cases with VHL mutation and those with VEGF expression were 760.80/mm2 and 715.95/mm2 respectively, both significantly higher than those in the cases without VHL-mutation and those without VEGF expression (547.03/mm2 and 437.44/mm2 respectively, all P = 0.001). The cases with expression of VEGF were divided into two groups according the presence or absence of VHL gene mutations or not. The MVD of the cases with VEGF expression and VHL mutation was 760.80 mm2, significantly higher than that of the cases with VEGF expression and without VHL mutation (547.03 mm2, P = 0.011). CONCLUSION: The mutation rate of VHL gene is high among the Chinese with sporadic CCRCC. VHL gene mutation increases significantly the VEGF expression, thus, and perhaps via other mechanism too, promoting the angiogenesis in tumor. The high level of MVD of the cases with VHL gene mutation may be related to the high malignant potential of CCRCC.

[Frequent somatic mutations of the von Hippel-Lindau (VHL) tumor suppressor gene and its meaning in sporadic human renal clear cell carcinoma].

OBJECTIVE: To investigate the mutation of VHL gene, an important tumor suppressor gene in primary sporadic human renal cell carcinoma (RCC) and analyse its relationships with pathological stage and grade of renal cell carcinoma. METHODS: We analyzed 57 cases of primary sporadic Chinese renal clear carcinoma using the polymerase chain reaction (PCR) and denaturing high performance liquid chromatography(DHPLC). All positive cases in DHPLC analysis were further characterized by direct sequencing. RESULTS: Somatic mutations were detected in 30 (53%) of 57 clear cell renal carcinomas including 13 deletions, 2 insertions, and 15 missense mutations. These mutations mainly occurred in the last one-third region of exon 1, 2,and 3. CONCLUSION: VHL tumor suppressor gene is one of the major tumor suppressor genes in human renal cell carcinoma and there are frequent mutations of VHL in primary sporadic Chinese renal clear cell carcinomas. The mutations of VHL gene were irrespective of the age and pathological grade and stage of patients.

[Somatic mutations of VHL gene and HIF-1alpha expression in primary renal clear cell carcinomas].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: Mutations of VHL gene may play a significant role in the tumorigenesis of RCC, and HIF-1alpha expression correlates with it.