Contrast-enhanced ultrasound using a time-intensity curve for the diagnosis of renal cell carcinoma

Study Type – Diagnosis (non‐consecutive series) Level of Evidence 3b What’s known on the subject? and What does the study add? In terms of imaging differentiation, distinguishing complex cystic renal masses that require surgery from those that do not remains a common and difficult diagnostic problem. Magnetic resonance imaging (MRI) is useful for characterizing complex cystic renal masses. But there are some cases that are difficult to diagnose differentially on computed tomography (CT) or MRI. We evaluated the usefulness of contrast‐enhanced ultrasound (CEUS) for the diagnosis of cystic renal cell carcinoma by using a time‐intensity curve (TIC). Assessments of blood flow in the solid component of a cystic tumour by CEUS using a second‐generation US contrast agent and TIC analysis have made it easier to objectively diagnose cystic renal cancer.

OBJECTIVE

• ? To evaluate the usefulness of contrast‐enhanced ultrasound (CEUS) for the diagnosis of renal cell carcinoma by employing a time‐intensity curve (TIC).

PATIENTS AND METHODS

• ? From May 2008 to October 2009, CEUS was performed prior to surgery in 30 patients with renal masses.
• ? In all, 10 of the 30 patients had cystic renal masses. The final diagnoses of all patients were pathologically confirmed. Contrast enhancement as a function of time was measured in two (tumour or solid component of cystic lesions and normal parenchyma) regions of interest (ROI) and TICs were obtained.
• ? The time to the contrast enhancement peak (TTP), intensity change from the baseline to peak (ΔI) and ΔI/TTP of the tumour and the normal parenchyma were measured from the TIC.

RESULTS

• ? Pathological diagnoses were renal cell carcinoma in 30 patients.
• ? The TTP of the cancer was shorter than that of the normal parenchyma in all cases (6.0 ± 2.0 vs 10.4 ± 3.0 s; P < 0.0001).
• ? The ΔI did not differ between the cancer and normal parenchyma [21.3 ± 5.9 vs 20.9 ± 7.0 decibels (db); P= 0.68]; the ΔI/TTP of the cancer was significantly higher than that of the normal parenchyma (3.9 ± 1.4 vs 2.2 ± 0.94 db/s; P < 0.0001).
• ? TIC patterns of solid cancer and cystic cancer were very similar.

CONCLUSIONS

• ? An objective and quantitative diagnosis of renal cell carcinoma by CEUS using a second‐generation ultrasound contrast agent can be made by employing a TIC.
• ? The TIC patterns of solid and cystic cancers were very similar, despite their morphological and vascular differences.
• ? CEUS using TIC is a promising tool in the diagnosis of cystic renal cancer.

     

CD105和VEGF在大肠癌新生血管中的表达

目的　探讨CD 10 5和血管内皮生长因子 (VEGF )在大肠癌新生血管中的表达及两者之间的关系。方法　采用鼠抗人CD10 5和免疫人VEGF单克隆抗体 ,通过免疫组化技术对 48例大肠癌手术切除标本及 48例远癌大肠组织的微血管密度 (MVD)及VEGF进行检测。结果　以CD10 5标记的大肠癌组织MVD及VEGF的表达与远癌组织间的差异具有非常显著性 (P <0 .0 1) ;大肠癌组织中MVD与VEGF的表达呈显著正相关 (P <0 .0 1) ;大肠癌组织MVD及VEGF的表达均与大肠癌的淋巴结转移、远处转移及Dukes分期有关 (P <0 .0 1)。结论　CD10 5和VEGF在大肠癌组织新生血管中均有良好表达 ,可作为大肠癌新生血管有价值的标志物。     

Angiogenesis and lymphangiogenesis in stage 1 germ cell tumours of the testis

OBJECTIVE: To determine whether angiogenesis can be used as an additional prognostic indicator in patients with stage 1 germ cell tumours of the testis. PATIENTS AND METHODS: Paraffin sections were assessed immunohistochemically from 51 patients with clinical stage 1 germ cell tumours of the testis (28 seminoma, 23 teratoma) treated by orchidectomy and surveillance only. Sections were analysed for microvascular density (MVD), and expression of the angiogenic factors vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). In addition, in the seminoma cases the presence of mRNA for the lymphangiogenic factor VEGF-C was examined by in situ hybridization, and its corresponding receptor VEGFR-3 by immunohistochemistry. RESULTS: Teratoma specimens had a significantly higher mean (range) MVD (85, 26-163; P < 0.01) than both seminoma (37, 16-91) and four normal specimens (26, 18-30). Teratoma specimens also had significantly higher VEGF expression than both seminoma and normal specimens (P < 0.01). Despite these differences between groups, and indeed individual tumours, there was no significant correlation between MVD and VEGF, or between either MVD or VEGF and relapse-free survival. TP expression was significantly greater in tumours than in normal specimens (P < 0.02) but with very little inter-tumour variation. VEGF-C mRNA and VEGFR-3 protein were detected in a third to a half of cases, with expression mostly around endothelial vessels. CONCLUSIONS: The marked differences between normal testis and tumours implicate angiogenesis in the biology of germ cell tumours of the testis. In addition, the detection of factors involved in lymphangiogenesis in some seminomas, tumours which initially metastasize primarily to lymph nodes, indicate that although not prognostic in this study, further studies are warranted in both these areas in the search for further prognostic indicators and therapeutic targets.     

Transrectal colour Doppler ultrasonography for quantifying angiogenesis in prostate cancer

OBJECTIVE: To assess the correlation between angiogenesis and Doppler signal intensity using transrectal colour Doppler ultrasonography (CDUS) in patients with prostate cancer. PATIENTS AND METHODS: The study comprised 56 patients who underwent radical prostatectomy and had untreated tumours with a volume of> 0.1 mL in the peripheral zone. CDUS images were recorded on videotape before surgery. The Doppler signal intensity in tumours was evaluated using the colour pixel intensity (PI). Microvessel density (MVD) and vascular endothelial growth factor (VEGF) immunoreactivity were determined in the prostatectomy specimens. Microvessels were identified by immunohistochemical staining of endothelial cells for CD31. RESULTS: The PI in the tumour correlated with MVD (P < 0.001) and increased with higher levels of VEGF immunoreactivity (P = 0.004). There was no correlation between Gleason score and MVD or PI in the tumour. CONCLUSION: Blood flow assessed by CDUS may reflect the state of angiogenesis in prostate cancer. CDUS may be a useful technique for predicting tumour progression or prognosis, and may be useful for monitoring the effects of anti-angiogenic agents in the future.     

Early immune biomarkers and intermediate‐term outcomes after heart transplantation: Results of Clinical Trials in Organ Transplantation‐18

Clinical Trials in Organ Transplantation‐18 (CTOT‐18) is a follow‐up analysis of the 200‐subject multicenter heart transplant CTOT‐05 cohort. CTOT‐18 aimed to identify clinical, epidemiologic, and biologic markers associated with adverse clinical events past 1 year posttransplantation. We examined various candidate biomarkers including serum antibodies, angiogenic proteins, blood gene expression profiles, and T cell alloreactivity. The composite endpoint (CE) included death, retransplantation, coronary stent, myocardial infarction, and cardiac allograft vasculopathy. The mean follow‐up was 4.5 ± SD 1.1 years. Subjects with serum anti‐cardiac myosin (CM) antibody detected at transplantation and at 12 months had a higher risk of meeting the CE compared to those without anti‐CM antibody (hazard ratio [HR] = 2.9, P = .046). Plasma VEGF‐A and VEGF‐C levels pretransplant were associated with CE (odds ratio [OR] = 13.24, P = .029; and OR = 0.13, P = .037, respectively). Early intravascular ultrasound findings or other candidate biomarkers were not associated with the study outcomes. In conclusion, anti‐CM antibody and plasma levels of VEGF‐A and VEGF‐C were associated with an increased risk of adverse events. Although this multicenter report supports further evaluation of the mechanisms through which anti‐CM antibody and plasma angiogenesis proteins lead to allograft injury, we could not identify additional markers of adverse events or potential novel therapeutic targets.     

Three‐dimensional endoanal ultrasonography of external anal sphincter defects in patients with faecal incontinence: correlation with symptoms and manometry

Aim Anal sphincter anatomy on two‐dimensional endoanal ‐ultrasonography (EUS) does not always correlate with the clinical data. The purpose of this study was to determine whether three‐dimensional (3D) measurements yield a better correlation. Method The study group included consecutive patients who underwent 3D EUS for faecal incontinence over a 2‐year period. The medical charts were reviewed for Cleveland Clinic Foundation Fecal Incontinence (CCF‐FI) score and manometric pressures. Endoanal ultrasonographic images were reviewed for the presence of an external anal sphincter (EAS) defect and its extent, as determined by the radial angle, length in the sagittal plane and percentage volume deficit. Correlational analyses were performed between the clinical and imaging data. Results Sixty‐one patients of median age 53 years (range 15–82) were evaluated. Thirty‐two patients had either a complete (17) or partial (15) EAS defect, and 29 patients had an intact sphincter. The CCF‐FI scores were similar in patients with and without an EAS defect (12.5 ± 5.6 and 11.4 ± 5.5, respectively). The intact‐sphincter group had a significantly greater EAS length (3 ± 0.4 vs 2 ± 0.62 cm, P = 0.02) and higher mean maximal squeeze pressure (MMSP; 99.7 ± 52.6 vs 66.9 ± 52.9 mmHg, P = 0.009). There were no statistically significant correlations between MMSP, CCF‐FI score and EAS status on 3D EUS. Mean percentage volume of the defect was similar in patients with complete and partial tears (14.5 ± 5.5 and 17.5 ± 7.2%, P = 0.25) and showed no correlation with physiological tests or symptom scores. Conclusion Improvements in external anal sphincter imaging have not yielded a better association with the clinical findings. The lack of clinical differences between patients with different EAS tears may reflect their similar volumetric defects.     

Prognostic Significance of Vascular Endothelial Growth Factor in Squamous Cell Carcinomas of the Tonsil in Relation to Human Papillomavirus Status and Epidermal Growth Factor Receptor

Background

Angiogenesis markers, vascular endothelial growth factor (VEGF) and microvessel density (MVD) have been associated with prognosis in squamous cell carcinomas (SCCs) of the head and neck. Other prognostic variables such as human papillomavirus (HPV) and epidermal growth factor (EGFR) may also be involved in tumour angiogenesis. This study determined relationships between VEGF, MVD, EGFR, HPV, response to radiotherapy and clinical outcome in 85 tonsillar SCCs.

Methods

HPV status was determined by an HPV multiplex real-time polymerase chain reaction (PCR) assay/p16 immunohistochemistry. Expression of VEGF, CD31 (as marker of MVD) and EGFR was assessed by semiquantitative immunohistochemistry.

Results

Strong VEGF expressers were significantly more likely to have higher MVD than were weak expressers. There were no associations between VEGF or MVD and gender, patient age, TNM stage, EGFR expression or HPV status. Tumours with MVD of >15 per high-power field were significantly more likely to be poorly differentiated. There was a significant inverse relationship between EGFR and HPV status. HPV was a strong independent marker of loco-regional recurrence and death. VEGF and EGFR were risk factors for local recurrence and disease-specific death on univariate analysis but the associations weakened after adjustment for HPV. Among patients treated with radiotherapy, VEGF was associated with disease-specific death after adjusting for HPV and TMN stage. High-VEGF-expressing tumours positive for EGFR had a worse prognosis than all other groups combined after adjusting for HPV and TNM stage.

Conclusions

HPV is a stronger prognostic marker than VEGF or EGFR in tonsillar SCCs. VEGF correlates with MVD in these tumours.     

Serum vascular endothelial growth factor-C and lymphoangiogenesis are associated with the lymph node metastasis and prognosis of patients with colorectal cancer

Background: The study aims to investigate the relationship among serum vascular endothelial growth factor (SVEGF‐C), VEGF‐C expression and lymph vessel density (LVD) in tumour tissue, and their influence to colorectal carcinoma (CRC). Methods: The SVEGF‐C concentration of 110 patients with CRC and 40 healthy donors was examined by ELISA. The 110 tumour tissues and 40 normal colorectal specimens were examined by immunohistochemical staining (SP method) with VEGF‐C and podoplanin (lymphatic vessel specific antibody). Kaplan–Meier survival analysis determined the influence on CRC prognosis. Results: CRC SVEGF‐C level (889.0 ± 264.0 pg/mL) significantly exceeded (P= 0.000) the control level (373.2 ± 97.3 ng/L), and was significantly higher in T3, lymph node metastasis (LNM), distant metastasis, and pTNM groups III and IV. LNM prediction sensitivity, specificity, and accuracy of SVEGF‐C were 85.7, 80.0 and 83.6%, respectively (875 pg/mL cut‐off). VEGF‐C expression was elevated in CRC versus control patients (P= 0.000), and was significantly related to LNM and pTNM stages III and IV. Mean LVD in CRC (6.3 ± 0.7/200 HP) significantly exceeded control mean (3.0 ± 0.7/200 HP) (P= 0.000). LVD was significantly higher in LNM and pTNM stages III and IV. SVEGF‐C level was significantly higher in VEGF‐C positive versus negative patients (P= 0.000), and was related to LVD (P= 0.009). Kaplan–Meier ranking of prognostic factors was SVEGF‐C level (P= 0.000), VEGF‐C expression (P= 0.001) and LVD (P= 0.012). Conclusion: SVEGF‐C level, VEGF‐C and LVD are related to LNM and poor prognosis in patients with CRC. SVEGF‐C may be a biomarker for LNM in CRC.     

Expression of vascular endothelial growth factor as a prognostic factor in node-positive squamous cell carcinoma in the thoracic esophagus: long-term follow-up study

Abstract To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) in squamous cell carcinoma in the thoracic esophagus, particularly as a prognostic factor, we have investigated the correlation between VEGF expression in tumor cells and microvessel density (MVD), pathologic factors, and survival. A total of 92 specimens, each from a thoracic esophageal squamous cell cancer patient who underwent transthoracic curative R0 esophagectomy between 1991 and 1994, were examined immunohistochemically using anti-human VEGF and anti-human von Willebrand factor antibodies. The incidence of VEGF expression in the tumor cells was relatively low, at 23.9% of all specimens. There was no significant correlation between VEGF expression and histopathologic factors. The MVD at the tumor margin in patients with VEGF-positive tumor cells was significantly greater than that in VEGF-negative cases (35.2 ± 8.9 vs. 22.7 ± 8.2). The survival rate for patients with VEGF expression was significantly lower than that of those without VEGF expression; the same situation was found in node-positive patients but not in node-negative patients. In addition, multivariate analysis revealed that VEGF expression was an independent prognostic factor in node-positive patients. VEGF may be implicated in the definition of the malignant phenotype of squamous cell esophageal cancer via tumor angiogenesis. Accordingly, VEGF expression in the tumor cells could be a useful prognostic factor for esophageal cancer, particularly in node-positive patients. Electronic Publication     

Changes in Lymphangiogenesis and Vascular Endothelial Growth Factor Expression by Neo‐Adjuvant Hormonal Therapy in Prostate Cancer Patients

BACKGROUND

The anti‐cancer mechanism of neo‐adjuvant hormonal therapy (NHT) is not well understood. Lymphangiogenesis plays an important role in cancer progression and is regulated by a complex mechanism that includes vascular endothelial growth factor (VEGF) signaling. However, there is little information regarding relationship between lymphangiogenesis and androgen deprivation. The aim of this study was to clarify changes in lymphangiogenesis and VEGF expression induced by androgen deprivation in prostate cancer in vivo and in vitro.

METHODS

Patients who had undergone a radical prostatectomy were enrolled in the study (NHT, n = 60 and non‐NHT, n = 64). Lymph vessels were identified by D2‐40 immunoreactivity and lymph vessel density and lymph vessel area (LVD and LVA, respectively) were measured from micrographs. The expression of VEGF‐A, ‐B, ‐C, and ‐D was evaluated by immunohistochemistry. The prognostic value of LVD and LVA for biochemical recurrence was also investigated.

RESULTS

Mean LVD ± SD was higher in the NHT than in the non‐NHT group (11.3 ± 3.0 vs. 7.1 ± 3.4 per high power field; P < 0.001). LVA was larger in the NHT than in the non‐NHT group (512.8 ± 174.9 vs. 202.7 ± 72.8 µm²; P < 0.001). VEGF‐A expression was lower whereas VEGF‐C and ‐D levels were higher in the NHT than in the non‐NHT group. VEGF‐B expression in specimens with NHT was lower than that in biopsy specimens at diagnosis. These results were confirmed by in vitro studies used androgen‐sensitive prostate cancer cell line. LVA was found to be an independent predictor of biochemical recurrence in patients who received NHT.

CONCLUSIONS

Our results demonstrate that NHT stimulates lymphangiogenesis via upregulation of VEGF‐C and ‐D, which may increase LVA and affect the outcome of prostate cancer patients. This findings were supported by in vitro data of prostate cancer cell. Prostate 77:255–262, 2017. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc.     

Assessment of local angiogenesis and vascular endothelial growth factor in the patients with atrophic-erosive and reticular oral lichen planus.

OBJECTIVES: The objective of this study was to assess local angiogenesis and expression of VEGF in atrophic-erosive and reticular oral lichen planus (OLP). STUDY DESIGN: Microvessel density (MVD) and VEGF level in 30 OLP subjects and 7 matched controls were detected by immunohistochemistry and ELISA. RESULTS: MVD and VEGF levels in whole OLP group were significantly elevated (P = .033, P < .0001, respectively), and there was a positive correlation between MVD and VEGF (correlation coefficient = 0.84, P < .0001). MVD in atrophic-erosive OLP was significantly higher than that in controls (P = .001) and reticular OLP (P = .042), and the expression of VEGF in both subgroups was significantly higher (P < .0001, P = .008, respectively) compared to control group. CONCLUSION: These results indicated that angiogenesis and VEGF expression were closely correlated to the different clinical forms of OLP lesions, which may give new insights into the mechanisms and treatment strategy of OLP.     

Testosterone and high‐sensitive C‐reactive protein in coronary artery disease patients awaiting coronary artery bypass graft

Natural androgens inhibit atherosclerosis in men. This study aimed to examine whether testosterone and high‐sensitive C‐reactive protein differ between patients with coronary artery disease and those without coronary artery disease and to determine the association with the severity of coronary artery disease. Two hundred and six male subjects were recruited. Serum total testosterone and high‐sensitive C‐reactive protein were estimated. Severity of coronary artery disease was assessed by angiographic scores. Total testosterone level in patients was significantly different from controls (11.4 ± 2.7 vs. 18.1 ± 7.2 nm P = 0.001) and high‐sensitive protein level in cases was significantly higher compared to controls (3.37 ± 1.62 mg l^?1 vs. 1.71 ± 0.60 mg l^?1, P = 0.001). Testosterone levels were not significantly different with vessel (P = 0.592), Leaman (P = 0.694) and Gensini (P = 0.329) score groups, but high‐sensitive C‐reactive protein showed significant positive correlation among the respective groups (P = 0.005, P = 0.028, P = 0.015). Testosterone was lower, while high‐sensitive C‐reactive protein was higher in patients compared to controls. Testosterone showed no correlation with the severity of atherosclerosis, but high‐sensitive C‐reactive protein showed significant positive correlation.     

As2O3碘油栓塞对兔VX2肝癌移植瘤凋亡、 增生及血管形成的影响

目的观察肝动脉As2O3碘油栓塞对兔肝移植瘤凋亡及增生细胞核抗原表达及微血管密度(MVD)的影响.方法 32只家兔肝内肿瘤种植后2周,随机分4组,经肝动脉插管分别给予不同处理,实验设生理盐水灌注组(A组)、单纯碘油栓塞组(B组)、阿霉素碘油栓塞组(C组)及As2O3碘油栓塞组(D组).治疗后1周,免疫组化方法测定肿瘤区的MVD值及增生细胞核抗原的表达,原位末端标记法检测肿瘤的凋亡指数.结果治疗后1周,单纯碘油栓塞及阿霉素碘油栓塞组,残余肿瘤区的MVD略有升高,与生理盐水对照组相比,统计学无显著性意义;As2O3碘油栓塞组残余瘤区MVD减低,与其他组相比差异具有显著性意义.各组凋亡指数和增殖指数分别为1.53±0.42、2.66±0.54、2.91±0.32、3.44±0.65和60.8±15.5、42.4±11.2、40.6±8.8、28.5±5.7,两者存在负相关.结论 As2O3碘油栓塞可以通过诱导肿瘤细胞凋亡,抑制肿瘤细胞增生发挥抗肿瘤效应,As2O3碘油栓塞可以抑制残余肿瘤的血管新生.     

Pancreatico‐jejunostomy decreases post‐operative pancreatic fistula incidence and severity after central pancreatectomy

Backgrounds

Central pancreatectomy (CP) is an alternative to pancreaticoduodenectomy and distal pancreatectomy in benign tumours of pancreatic isthmus management. It is known for a high post‐operative pancreatic fistula (POPF) rate. The purpose of this study was to compare POPF incidence between pancreatico‐jejunostomy (PJ) and pancreatico‐gastrostomy (PG).

Methods

Fifty‐eight patients (mean age 53.9 ± 1.9 years) who underwent a CP in four French University Hospitals from 1988 to 2011 were analysed. The distal pancreatic remnant was either anastomosed to the stomach (44.8%, n = 25) or to a Roux‐en‐Y jejunal loop (55.2%, n = 35) with routine external drainage allowing a systematic search for POPF. POPF severity was classified according to the International Study Group on Pancreatic Fistula (ISGPF) and Clavien‐Dindo classifications.

Results

The groups were similar on sex ratio, mean age, ASA score, pancreas texture, operative time and operative blood loss. Mean follow‐up was 36.2 ± 3.9 months. POPF were significantly more frequent after PG (76.9 versus 37.5%, P = 0.003). PG was associated with significantly higher grade of POPF both when graded with ISGPF classification (P = 0.012) and Clavien‐Dindo classification (P = 0.044). There was no significant difference in post‐operative bleeding (0.918) and delayed gastric emptying (0.877) between the two groups. Hospital length of stay was increased after PG (23.6 ± 3.5 days versus 16.5 ± 1.9 days, P = 0.071). There was no significant difference in incidence of long‐term exocrine (3.8 versus 19.2%, P = 0.134) and endocrine (7.7 versus 9.4%, P = 0.575) pancreatic insufficiencies.

Conclusion

PG was associated with a significantly higher POPF incidence and severity in CP. We recommend performing PJ especially in older patients to improve CP outcomes.     

Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma

OBJECTIVE

To clarify the significance of microvessel density (MVD) in a retrospective investigation the relationship between the pattern of MVD (reflecting angiogenesis), and tumour stage, grade, size, and occurrence of microvessel invasion (MVI), metastasis, and cancer‐specific survival (CSS) in patients who had surgery for renal cell carcinoma (RCC).

PATIENTS AND METHODS

Vessels were labelled in sections of formalin‐fixed, paraffin‐embedded tissues from 54 RCCs by CD34 immunohistochemistry. The mean MVD, expressed as the number of vessels per 10 high‐power fields (HPF, ×400) were measured for each case. In addition, all pathological slides were reviewed for the presence and absence of MVI. The prognostic value of MVD and MVI was then evaluated, and correlated with the usual prognostic variables, tumour metastasis and CSS.

RESULTS

In a univariate analysis of CSS, the MDV tended to be lower as stage increased from pT1 to pT3, and as grade increased from G1 to G4, although it was statistically significant only for stage (P < 0.001 and 0.050, respectively). The mean MVD was higher in 42 nonmetastatic than in 12 metastatic tumours, and in 33 tumours associated with MVI than in 21 with no MVI (P < 0.001). The mean MVD was also lower and significantly different for 28 large than 26 small tumours (P = 0.005). The survival rate of patients with tumours that were small, low‐stage, of higher MVD, with no MVI and metastasis was significantly higher than that of patients with large, high‐stage, low MVD, with MVI and metastatic tumours (all P < 0.001). MVI was significantly more common with a decreasing trend in MVD and the presence of metastasis (Spearman rank correlation r_s = ?0.68, P = 0.01, and r_s = 0.39, P = 0.01, respectively). Independent prognostic factors in a multivariate analysis were: in all patients with RCC, tumour stage (P = 0.013) and metastasis (P = 0.028); in those with low MVD, MVI (P = 0.004) and metastases (P = 0.016); in those with no MVI, stage (P = 0.020); in those with MVI, MVD (P = 0.001); in those with no metastases, stage (P = 0.045); and in those with metastases, MVD (P < 0.001). No independent predictor was identified in patients with high MVD. In patients with no metastases there was a significantly shorter median CSS time in RCCs with low MVD and with MVI (P = 0.004 for both). Similarly, patients who had grade 3–4 tumours, vs those with lower MVD and with MVI, had a significantly shorter median CSS (P = 0.020 for MVD, and 0.01 for MVI).

CONCLUSIONS

This study suggested that MVD in RCC was inversely associated with MVI, tumour metastasis, patient survival and tumour diameter and stage, from the usual prognostic variables, but MVD was not an independent prognostic factor in multivariate analysis for all patients with RCC. Low MVD and the presence of MVI appears to be a marker for identifying patients with an adverse prognosis.     

Short‐term and long‐term outcomes of patients with malignant large bowel obstruction

Objective: The aim of the present study was to review our experience in the surgical management of patients with obstructing colorectal cancers over an 11‐year period, 1987–1997. Patients and methods: Retrospective review of case records of 275 patients (male: 177; female 98) who had undergone emergency surgery for obstructing colorectal cancers was performed. Tumours proximal to splenic flexure were defined as proximal tumours while those at or below the splenic flexure were defined as distal tumours. Results: The obstruction was caused by proximal tumours in 88 (32%) patients. The resection rate and the primary anastomotic rate were higher for proximal tumours compared with distal tumours (95.5%vs 85.6%, P = 0.014; 92%vs 30.5%, P < 0.001). For distal tumours, stoma rate was found to be influenced by the following factors: preoperative albumin level, duration of observation after admission, operating surgeons’ years of experience, bowel perforation and site of the obstructing tumour. Multivariate analysis disclosed that surgeons’ experience was the only independent factor predicting stoma formation. The in‐hospital mortality and the anastomotic leakage rates were 15.3% and 5.6%, respectively. Tumour stage was the only prognostic factor affecting the disease‐free survival after curative resection. The 5‐year disease‐free survival rates for Dukes’ B and C disease were 66% and 37.2%, respectively. Conclusions: Tumour stage was a significant prognostic factor for patients with obstructing colorectal cancers. Emergency surgery for distal tumours should preferentially be performed by more experienced surgeons in order to achieve a higher anastomotic rate.     

CD105在结直肠癌中的表达及其临床意义

目的探讨CD105在结直肠癌中的表达及其作为肿瘤新生血管标记物的临床价值。方法采用鼠抗人CD105单克隆抗体(MAb),应用免疫组织化学技术检测48例结直肠癌手术切除标本及48例对照组织的微血管密度(MVD),并以Ⅷ因子相关抗原(F-8RAg)及血管内皮生长因子(VEGF)的表达作为对照研究。结果(1)MVD及VEGF在结直肠癌组织与对照组织间表达的差异具有非常显著性意义(P<0.001,P<0.01);(2)以CD105和F-8RAg测得的MVD差异具有非常显著性意义(P<0.001);(3)VEGF在结直肠癌的表达与CD105的表达呈显著正相关(P<0.01),而与F-8RAg的表达无关(P>0.05)。结论CD105在结直肠癌组织新生血管有良好表达,可以作为结直肠癌新生血管有价值的标志物。以CD105测得的MVD可以被认为是与肿瘤生长、转移及预后有关的一种重要指标。     

The role of SMAD4 in early‐onset colorectal cancer

Objective Chromosomal loss within the region of 18q and loss of SMAD4 expression have been reported to be frequent somatic events during colorectal cancer tumour progression; however, their associations with age at onset have not been widely studied. Method We analysed 109 tumours from a population‐based case‐family study based on colorectal cancers diagnosed before the age of 45 years. These patients with early‐onset colorectal cancer had been previously screened for germ‐line mismatch repair gene mutations, microsatellite instability (that included the mononucleotide repeat in TGFβRII) and somatic k‐ras mutations. We measured SMAD4 protein expression using immunohistochemistry and SMAD4 copy number using quantitative real‐time PCR. Results Loss of SMAD4 protein expression was observed in 27/109 (25%) of cancers tested and was more commonly observed in rectal tumours (15/41, 36%) when compared with tumours arising in the colon (11/66, 17%) (P = 0.04). There was no association between SMAD4 protein expression and TGFβR11 mutation status, SMAD4 copy number, family history, MSI status, tumour stage or grade. Conclusion Loss of SMAD4 expression is a common feature of early‐onset colorectal tumours as it is in colorectal cancers diagnosed in other age‐groups. Taken together, the molecular pathways (genetic and epigenetic) now known to be involved in early‐onset colorectal cancer only explain a small proportion of the disease and require further exploration.     

TUMOUR CELL WOUND DISTRIBUTION AFTER COLECTOMY IN A PORCINE MODEL

Background: Concerns over tumour implants have impeded the adoption of laparoscopic surgery for cancer. Explanations assume an increased number of malignant cells present in trocar wound sites. The following are tested in the present paper: (i) that the magnitude of wound contamination following surgery is related to the location of the tumour cells; and (ii) the surgical approach. Methods: We have used porcine sigmoid colectomy model to compare the number of tumour cells on laparoscopic wounds after resections in the presence of intraluminal, intramural and intraperitoneal ⁵¹Cr-labelled, fixed HeLa tracer cells. Open colectomies were also performed in the presence of intraperitioneal tracer cells and their numbers on laparotomy wound surfaces were determined by gamma counting. Results: With intraperitoneal cells, laparotomies had 1087 (± 106) tracer cells per mm (n= 4) while trocar wounds had 103 (± 54) cells per mm (n= 10) (P > 0.05). Resection of intramural tumours resulted in lower trocar wound contamination (0.9 ± 0.6 cells/mm, n= 3). Resection of colon including intraluminal tracer cells resulted in 2.9 ± 2.1 cells/mm on trocar wounds (n= 3). Conclusions: More tumour cells were deposited on open than laparoscopic trocar wound surfaces. Also, the risk of wound implantation is less with intraluminal or intramural tumours than with intraperitoneal cells (P > 0.05).     

TNF‐α–induced NF‐κB signaling reverses age‐related declines in VEGF induction and angiogenic activity in intervertebral disc tissues

We previously demonstrated that VEGF and its receptors were expressed in human herniated discs (HD). TNF‐α induced VEGF, resulting in neovascularization of disc tissues in a model of HD. The goal of the current research was to investigate the precise role of TNF‐α–induced VEGF and the mechanism of angiogenesis in disc tissues. We performed ELISAs, Western blots, and immunohistological examinations to assess the role of TNF‐α–induced VEGF using organ disc cultures with wild type, TNF receptor 1‐null (TNF‐RI^null), or TNF receptor 2‐null (TNF‐RII^null) mice. VEGF induction was inhibited when we used TNF‐RI^null‐derived disc tissues. NF‐κB pathway inhibitors also strongly suppressed VEGF induction. Thus, TNF‐α induced VEGF expression in disc cells primarily through the NF‐κB pathway. In addition, VEGF immunoreactivity was detected predominantly in annulus fibrosus cells and increased after TNF‐α stimulation. TNF‐α treatment also resulted in CD31 expression on endothelial cells and formation of an anastomosing network. In contrast, angiogenic activity was strongly inhibited in the presence of NF‐κB inhibitors or anti‐VEGF antibody. Our data show angiogenesis activity in disc tissues is regulated by VEGF and the NF‐κB pathway, both of which are induced by TNF‐α. The level of angiogenic activity in disc tissues was closely related to aging. Because neovascularization of HD is indispensable for HD resorption, the prognosis of HD and the rate of the resorption process in patients may vary as a function of the patient's age. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:229–235, 2009