Hypervascular Group Research Articles

Outcomes and Role of Lymphadenectomy in Hypervascular Intrahepatic Cholangiocarcinoma Based on CT-Vascularity.

This study aimed to evaluate the outcomes and role of lymphadenectomy in hypervascular intrahepatic cholangiocarcinoma (ICC) quantified using the arterial phase of contrast-enhanced computed tomography (CT). Consecutive patients with mass-forming (MF) or predominantly MF type ICC who underwent surgical resection from 2000 to 2019 were retrospectively analyzed. Using the image of the late arterial phase, CT-vascularity was calculated by dividing the CT value of the tumor (Hounsfield units) with that of the liver parenchyma. According to the CT-vascularity, patients were divided into hypervascular (CT-vascularity>1) and non-hypervascular (CT-vascularity≤1) groups. Clinicopathologic features and survival outcomes were compared between the two groups. Further, the prognostic impact of lymphadenectomy was assessed in the hypervascular group. Of the 135 patients with MF-ICC, the hypervascular group, and non-hypervascular group comprised 47 (34.8%) and 88 patients (65.2%), respectively. The hypervascular group displayed clinical features typically associated with hepatocellular carcinoma (HCC) (i.e., viral hepatitis or history of HCC) and less aggressive tumor characteristics such as lower proportions of regional lymph node metastasis. The overall survival (OS) and recurrence-free survival (RFS) of the hypervascular group were significantly better than those of the non-hypervascular group (all, p<0.001), and these results were retained after adjusting for known prognostic factors. Further, implementation of lymphadenectomy was not associated with benefit for OS and RFS in the hypervascular group (p=0.819, p=0.912). Hypervascular ICC itself represents a favorable prognosis, and there is a possibility of omitting lymphadenectomy in this subgroup.

Computed Tomography Perfusion Combined With Preoperative Embolization for Reducing Intraoperative Blood Loss in Separation Surgery for Thoracolumbar Metastases.

A prospective consecutive case study. This study aimed to assess the accuracy of computed tomography perfusion (CTP) in evaluating the vascularity of thoracolumbar metastases and to determine the impact of combining CTP with preoperative embolization on reducing intraoperative blood loss during separation surgery. Surgery for thoracolumbar metastases is a complex procedure with the potential for substantial blood loss. Therefore, assessing tumor vascularity before surgery and taking measures to minimize intraoperative blood loss is essential. A total of 62 patients with thoracolumbar metastases were prospectively enrolled. All patients underwent separation surgery using the posterior approach. Before surgery, the vascularity of the metastases was evaluated using CTP. On the basis of the CTP results, patients were categorized into hypervascular and hypovascular groups. Preoperative angiography and embolization were performed for the hypervascular group. Clinical data were abstracted, including intraoperative blood loss, perioperative complications, visual analog scale score, neurological status, and the accuracy of vascularity evaluation by CTP confirmed by angiography. χ 2 testing was used to compare categorical variables, whereas independent sample t tests were used to compare continuous variables, with paired t tests used to assess differences from preoperative to postoperative time points. The mean intraoperative blood loss was 485±167 and 455±127.6mL in the two groups, respectively. The accuracy of vascularity evaluation by CTP was 100%. In the hypervascular group, 80.6% of the patients experienced at least one level of improvement in neurological status, while the hypovascular group had 81.5% of patients with similar improvement. None of the patients experienced neurological deterioration. There was a significant reduction in visual analog scale scores in both groups after the operation. The vascularity of thoracolumbar metastases could be accurately evaluated using noninvasive CTP. When combined with preoperative embolization, this approach effectively and safely reduced intraoperative blood loss in the setting of separation surgery.

Arterial enhancement pattern predicts survival in patients with resectable and unresectable intrahepatic cholangiocarcinoma

BackgroundIn patients undergoing resection of intrahepatic cholangiocarcinoma (ICC), hypervascularity during the arterial phase of contrast-enhanced computed tomography (CT) is associated with better prognosis than hypovascularity. However, the prognostic implications of arterial enhancement pattern in patients with unresectable ICC are unknown. We assessed the prognostic implications of arterial enhancement pattern in patients with resectable and unresectable ICC. MethodsConsecutive patients who underwent surgery or gemcitabine-plus-cisplatin chemotherapy for ICC during 2003–2015 and CT with dynamic enhancement for diagnosis were included. After review by 2 radiologists, tumors were categorized according to the percentage of the tumor exhibiting arterial enhancement as hypervascular (>50% of tumor exhibiting enhancement), peripherally enhancing (10%–50%), and hypovascular (<10%). In each cohort (surgical and medical), overall survival (OS) curves were generated using the Kaplan-Meier method, and differences between curves were evaluated with Cox analysis. ResultsThe study included 56 patients treated surgically and 89 patients with unresectable ICC. Mean (standard deviation) tumor density in the hypervascular, peripherally enhancing, and hypovascular groups was 119.3 (45.2) Hounsfield units (HU), 72.1 (15.9) HU, and 59.9 (14.4) HU, respectively, in the surgical cohort and 93.6 (17.5) HU, 66.6 (16.2) HU, and 48.7 (14.3) HU, respectively, in the medical cohort. In both cohorts, the 5-year OS rate was significantly higher in the hypervascular group than in the hypovascular group (surgical, 67.6% vs 22.5%, P = .038; medical, 15.4% vs 0%, P = .030). In both cohorts, a Cox proportional hazards model analysis showed that hypervascularity was significantly associated with better OS. ConclusionHypervascularity during the arterial CT phase is a prognostic biomarker in patients undergoing ICC resection and patients with unresectable ICC.

The Diagnostic Value of Superb Microvascular Imaging in Prediction of Uterine Artery Embolization Treatment Response in Uterine Leiomyomas.

We aimed to determine if superb microvascular imaging (SMI) can predict response to uterine artery embolization (UAE) as compared with power Doppler ultrasound. The blood flow and the volume of the dominant leiomyoma was evaluated by power Doppler ultrasonography (PDUS) and SMI 1 day before and 3 months after the UAE procedure. SMI and PDUS blood flow were classified to 4 grades of vascularity. The change in fibroid volume in Grades 0-2 (hypovascular group) was compared to the hypervascular Grade 3 group. Twenty-eight women (mean age, 40.9 years; range, 33-53 years) were examined with PDUS and SMI before and 3 months after UAE. The volume reduction was statistically significantly higher hypervascular group (P < .05). When we accept 30% or more volume reduction as a good response to UAE, the positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of SMI were 100, 64, 73.6, 100, and 82.1%, respectively. There was excellent agreement between the two blinded observers in SMI measurements. SMI, with its high reproducibility, provides further microvessel information than PDUS in uterine fibroids. It may be a useful tool in prediction of response to UAE treatment and improve counseling and patient selection for UAE versus medical or surgical treatment options.

Short-term efficacy of iodine-125 radioactive seed implantation therapy for hypoxic tumors

Objective To study the short-term efficacy of computed tomography (CT)-guided iodine-125(125I) radioactive seed implantation in the treatment of hypoxic tumors. Methods Twenty-two patients treated with 125I radioactive seed implantation in our department from 2014 to 2016 were divided into hypovascular tumor group (hypoxic group, n=12) and hypervascular tumor group (non-hypoxic group, n=10) based on the hemodynamics of solid tumor evaluated by color Doppler ultrasound. The enhanced CT images were loaded to the three-dimensional particle implantation planning system for preoperative planning. After 125I radioactive seed implantation, the D90 for target volume was verified to be 106-128 cGy. Treatment outcomes were evaluated according to the World Health Organization criteria at 1-3 months after surgery. Results In all the patients, the overall response rate was 82% at 3 months after surgery. There were no significant differences in response (complete response+ partial response) rates at 1, 2, or 3 months after surgery between the hypoxic group and the non-hypoxic group (P=0.840, 0.696, 0.840). Conclusions In the treatment of solid malignant tumor, 125I radioactive seed implantation can overcome the resistance of hypoxic tumor to radiotherapy in vitro and achieve satisfactory short-term efficacy. Key words: Iodine-125 radioactive seed; Hypoxic tumor; Short-term efficacy

Characterization of Skull Base Lesions Using Pseudo-Continuous Arterial Spin Labeling.

Pseudo-continuous arterial spin labeling (pCASL) is anon-invasive magnetic resonance (MR) perfusion technique. Our study aimed at estimating the diagnostic performance of the pCASL sequence in assessing the perfusion of skull base lesions both qualitatively and quantitatively and at providing cut-off values for differentiation of specific skull base lesions. In this study 99 patients with histopathologically confirmed skull base lesions were retrospectively enrolled. Based on a pathological analysis, the lesions were classified as hypervascular and non-hypervascular. Patients were divided into two subgroups according to the anatomical origin of each lesion. The MRI study included pCASL and 3D T1-weighted fat-saturated post-contrast sequences. Of the patients seven were excluded due to technical difficulties or patient movement. The lesions were classified by two raters, blinded to the diagnosis as either hyperperfused or non-hyperperfused, based on the pCASL sequence. The normalized tumor blood flow (nTBF) of each lesion was determined. Qualitative and quantitative characteristics of hypervascular and non-hypervascular lesions were compared. Visual assessment enabled correct classification of 98% of the lesions to be performed. Quantitatively, we found significant differences between the nTBF values for hypervascular and non-hypervascular lesions (p< 0.001) and provided cut-off values, allowing meningioma and schwannoma to be distinguished from meningioma and adenoma. Significant differences were also found within the hypervascular group, namely, paraganglioma was more hyperperfused than meningioma (p= 0.003) or metastases (p= 0.009). The present study demonstrates the high diagnostic performance of pCASL in characterizing skull base lesions by either visual assessment or nTBF quantification. Adding the pCASL sequence to the conventional protocol of skull base assessment can be recommended.

Evaluation of hepatocellular carcinoma tumor vascularity using contrast-enhanced ultrasonography as a predictor for local recurrence following radiofrequency ablation

PurposeThe purpose of this study was to evaluate whether the hypervascularity of hepatocellular carcinomas (HCCs) on contrast-enhanced ultrasonography (CEUS) prior to radiofrequency ablation (RFA) is a significant risk factor for local recurrence after RFA. Materials and methodsInstitutional review board approval and informed consent were obtained. Overall, 208 patients (mean age, 71.7 years; range, 50–87 years; 137 men, 71 women) with 282 HCCs treated with RFA were analyzed retrospectively. The mean maximum tumor diameter was 15.7mm. We compared the abilities of CEUS and contrast-enhanced computed tomography (CECT) to detect hypervascularity in HCCs. We then classified the HCCs into two groups according to the arterial-phase CEUS findings: a “hypervascular group” with whole or partial hypervascular areas within the lesions compared with the surrounding liver parenchyma, and a “non-hypervascular group” with isovascular or hypovascular areas within the lesions. We assessed the cumulative rate of local recurrence after RFA, and we also evaluated the risk factors for local recurrence using a univariate analysis. ResultsThe detection rate for hypervascular HCCs was significantly higher using CEUS (78%, 221/282) than that using CECT (66%, 186/282) (P<0.001). Using the CEUS findings, the cumulative rate of local recurrence was significantly higher in the hypervascular group (41.2%, 56/221) than in the non-hypervascular group (18.4%, 6/61) (P=0.007). A univariate analysis revealed that hypervascularity on CEUS was an independent risk factor for local recurrence (P=0.010). ConclusionHypervascularity in HCCs as observed using CEUS is a significant risk factor for local recurrence after RFA.

Combined hepatocellular-cholangiocarcinoma: Gadoxetic acid-enhanced MRI findings correlated with pathologic features and prognosis.

To evaluate gadoxetic acid-enhanced magnetic resonance imaging (MRI) findings of combined hepatocellular cholangiocarcinoma (cHCC-CC) with special emphasis on correlation of MRI findings with histopathologic tumor characteristics and survival outcomes after curative surgery. Our Institutional Review Board approved this study, with a waiver of informed consent. For 82 patients (64 men, 18 women; mean age, 54.0 years; age range, 30-81) with surgically confirmed cHCC-CCs, we evaluated clinical features, histologic findings, and tumor morphologic and enhancement features on gadoxetic acid-enhanced liver MRI at 1.5T (n = 67) or 3.0T (n = 15). Imaging features of cHCC-CCs were correlated with pathologic findings according to the 2010 World Health Organization classification system. Tumors were categorized as hypervascular or nonhypervascular based on arterial phase enhancement and were compared with respect to overall and recurrence-free survival after curative-intent surgery. Of the 82 lesions, 48 showing global arterial phase enhancement were categorized as the hypervascular group, while 34 lesions demonstrating rim, peripheral, or isoenhancement were categorized as the nonhypervascular group. There was no significant difference in MRI findings between pathologic tumor types (classical type versus stem cell feature type, P = 0.324-1.0). Compared with the nonhypervascular group, the hypervascular group had a larger HCC component (P = 0.014), smaller CC component (P = 0.001), and lesser amount of fibrotic stroma (P = 0.006) on pathologic analysis and was an independent factor associated with better overall survival after surgical resection (P = 0.033). Gadoxetic acid-enhanced MRI findings of cHCC-CCs were diverse, reflecting heterogeneous histologic features. The hypervascular group on MRI is associated with a larger HCC component, smaller CC component, less fibrotic stroma, and better overall survival after curative surgery than the nonhypervascular group. 4 J. MAGN. RESON. IMAGING 2017;46:267-280.

Mass-forming intrahepatic cholangiocarcinoma: Enhancement patterns in the arterial phase of dynamic hepatic CT - Correlation with clinicopathological findings

To evaluate the relationship between the enhancement pattern of intrahepatic cholangiocarcinomas (ICCs) in the hepatic arterial phase (HAP) of dynamic hepatic CT and the clinicopathological findings with special reference to the perihilar type and the peripheral type. Forty-seven patients with pathologically proven ICCs were enrolled. Based on the enhancement pattern in the HAP, the lesions were classified into three groups: a hypovascular group (n=13), rim-enhancement group (n=18), and hypervascular group (n=16). The clinicopathological findings were compared among the three groups. Perihilar-type ICCs were significantly more frequently observed in the hypovascular group than in the rim-enhancement and hypervascular groups (p=0.006 and p <0.001, respectively). Lymphatic invasion, perineural invasion, and biliary invasion were significantly more frequent in the hypovascular group than the rim- enhancement group (p=0.001, p=0.025 and p=0.029, respectively) or hypervascular group (p <0.001, p <0.001 and p=0.025, respectively). Patients with hypovascular lesions showed significantly poorer disease-free survival than patients with rim-enhancing or hypervascular lesions (p=0.001 and p=0.001, respectively). Hypovascularity was an independent preoperative prognostic factor for disease-free survival (p<0.001). Hypovascular ICCs in the HAP tend to be of perihilar type and to have more malignant potential than other ICCs. • Hypovascular ICCs have greater malignant potential than rim-enhancing and hypervascular ICCs. • Hypovascular ICCs show a higher frequency of perihilar-type ICCs. • Perihilar-type ICCs do not always display distal ductal wall thickening.

The favorable prognosis after operative resection of hypervascular intrahepatic cholangiocarcinoma: A clinicopathologic and immunohistochemical study

The aim of this study was to clarify the clinicopathologic characteristics of hypervascular intrahepatic cholangiocarcinoma (ICC). Seventy patients with a mass-forming type ICC underwent hepatectomy between 2003 and 2013. These patients were divided into 2 groups and compared based on findings during the late arterial phase of computed tomography: hypervascular ICC (the mean computed tomography value of the tumor≥that of the nontumorous liver parenchyma, n=21), and hypovascular ICC (n=49). The overall survival of the hypervascular group was better than that of the hypovascular group (5-year survival: 63% vs 35%, respectively, P=.046). Pathologic examinations showed less lymph node metastasis (0% vs 39%), lymphatic invasion (14% vs 57%), mucin secretion (19% vs 61%), tumor necrosis (24% vs 57%), and combined periductal infiltration (0% vs 27%), P≤.01 each, in the hypervascular group. The microscopic bile ductular feature was more frequent in the hypervascular group (57% vs 29%, P=.023). Immunohistochemical analysis revealed that the hypervascular group had greater immunoreactivity to neural cell adhesion molecule (71% vs 37%, P=.008) and a lesser S100P immunoreactivity (33% vs 73%, P=.002). Multivariate analysis revealed that neural cell adhesion molecule reactivity (P=.018) was independently associated with the hypervascular group. Tumor vascularity predicts the aggressiveness of ICC. In most patients with hypervascular ICC, the tumor has a less invasive nature. Furthermore, the prognosis after resection in patients with hypervascular ICC is significantly better than in patients with hypovascular ICC.

Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm

To clarify the biological behaviour of small hypovascular hepatocellular carcinoma (HCC) because of insufficient evidence even though frequently encountered. The study covered naïve 4,474 patients who met solitary HCC ≤ 3 cm (mean, 2.1 cm), histopathologically proven and Child Pugh A or B. Macroscopic vascular invasion and distant metastasis were excluded. The hypovascularity of tumour was defined as hypo- or iso-enhancement in arterial phase of multiple dynamic imaging techniques. Of them, 802 (18%) were hypovascular. The ratio of hypovascular HCC decreased as tumour size increased (P < 0.001) and most of them developed to hypervascular type when they grew over 1.5 cm. Hypovascular group showed a significantly higher ratio of well differentiated grade (P < 0.001) and marginally less incidence of microvascular invasion and metastases compared with hypervascular group. The histologic dedifferentiation (less differentiation) developed step-by-step as tumour size increased in hyper- and even hypovascular group. The des-γ-carboxy prothrombin (DCP) value ≥ 300 mAU/ml was closely correlated with increase of tumour size in both groups. Logistic regression analysis revealed five variables were independent predictors for hypovascular HCC; tumour size ≤ 1.5 cm, alpha-fetoprotein < 200 ng/ml, DCP < 40 mAU/ml, well differentiated grade, and positivity for hepatitis C virus antibody. Hypovascular HCC was biologically less aggressive and developed with stepwise dedifferentiation and transformation to hypervascular appearance along with tumour growth. These results will help in leading correct diagnosis of small hypovascular tumour and assessing optimal treatment for hypovascular HCC ≤ 3 cm.

Cyclooxygenase-2 expression determines neo-angiogenesis in gallbladder carcinomas.

Neo-angiogenesis may have an important role in the poor prognosis of gallbladder carcinoma. An enhanced expression of COX-2 was found in precancerous lesions and in gallbladder carcinoma, likely to be involved in carcinogenesis as well as in angiogenesis. To study the relationships between the COX-2 expression and degree of vascularization, as well as to evaluate their role in the prognosis of patients with gallbladder carcinoma. 27 cases of gallbladder adenocarcinoma were included, classified grading I-III according the WHO classification. The COX-2 and endothelial antigen CD105 expressions were assessed immunohistochemically. COX-2 expression was evaluated according to the percentage and staining intensity of positive cells into "COX-2 positive" and "COX-2 negative" groups. In order to assess tumor microvessel density (MVD), CD105 positively stained microvessels were counted for each specimen in predominantly vascular areas (hot spots) at 200 x magnification. The MVD ranged from 9 to 46 microvessels/field. 15 tumors belonged to the hypervascular group (MVD > or = 25) and 12 to the hypovascular group. There were 16 (59.2%) COX-2 positive cases. There was difference in the degree of angiogenesis between COX-2 positive vs. COX-2 negative group: 11 (68.8%) out of 16 "COX-2 positive" tumors were hypervascular, in comparison with just 4 (36.4%) of "COX-2 negative" tumors. Our data show that the MVD corresponds to the COX-2 overexpression in gallbladder carcinomas. Augmented tumor neovascularization induced by COX-2 might be responsible for the poor prognosis in gallbladder carcinoma patients.

Angiogenesis in advanced colorectal adenocarcinoma with special reference to tumoral invasion.

Angiogenesis is a crucial step in tumor growth and progression. Its quantification by microvessel counting has a prognostic value in several types of malignancies and recently has been appraised in gastrointestinal tumors. To assess the prognostic significance of microvessel quantification in colorectal carcinomas, studying its association with hematogenous metastases, survival and clinicopathological variables such as size, histologic differentiation and depth of tumoral invasion. Forty eight patients with colorectal adenocarcinoma were included in this study. Histologic sections of invasion tumoral margin (4 microns) were analyzed and endothelined microvessels were immunostained with monoclonal mouse Von Willebrand Factor (anti-FVIII). The microvessel count was performed from the identification of the area with increased microvessel density--hot spots--and results of the mean in five of these fields. The cut-off microvessel count was 14 microvessels/0.785 mm2, which divided the sample into hypovascular and hypervascular groups. While 2/8 (25%) tumors with muscularis propria invasion were classified as hypervascular, 11/15 (73%) tumors with serosa or perivisceral fat were classified as hypervascular. However, a non-significant statistical association was found between the angiogenesis quantification, hematogenous metastases, survival and clinicopathological variables such as size and histologic differentiation of the tumor. The findings of significantly increase of microvessel count in conformity with tumoral invasion depth supports the hypothesis that tumor progression might be related to angiogenesis. Although angiogenesis is an important step in the tumoral growth and during the metastatization process, other factors can be implicated.

Implications of human macrophage metalloelastase and vascular endothelial growth factor gene expression in angiogenesis of hepatocellular carcinoma.

To determine molecular mechanisms involved in angiogenesis of hepatocellular carcinoma (HCC). Tumor angiogenesis is believed to derive from the balance between angiogenic stimulators and inhibitors. It has been suggested that the switch to the angiogenic phenotype requires both upregulation of the first and downregulation of the second. However, its molecular basis in vivo remains obscure. In this study the authors analyze the participation of two factors in angiogenesis of HCC- human macrophage metalloelastase (HME), a matrix metalloproteinase responsible for the generation of angiostatin, a potent angiogenesis inhibitor, and vascular endothelial growth factor (VEGF), the most potent endogenous angiogenic factor. Tumorous and contiguous nontumorous tissues from 25 patients with HCC who underwent curative partial hepatectomy were subjected to Northern blot analysis to detect HME and VEGF messenger RNA (mRNA) expression. Western blot analysis was used to detected angiostatin. Tumor vascularity was evaluated using hepatic angiography. Eleven of the 15 cases expressing the HME gene showed hypovascular tumors, whereas hypervascular tumors were seen in 9 of the 10 HME-negative cases. The median of HME mRNA expression (tumorous/nontumorous ratio) was 6.5 (range 0-264.5) in the hypovascular group and 0 (range 0-3.2) in the hypervascular group. A stepwise logistic analysis revealed that HME and VEGF mRNA expression were two independent variables significantly affecting the vascularity of HCC tumors. HME gene expression is significantly associated with hypovascular tumors; moreover, angiogenesis in HCC is not determined by a single factor, but depends on the net balance between HME and VEGF gene expressions.

The prognostic significance of tumor vascularization in patients with localized colorectal cancer

Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a x200 field in the area of the most dense neovascularization. Vascular density was found to be 75+/-27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (>75) than in those of less vessel density (<75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.

Microvessel density of hepatocellular carcinoma: its relationship with prognosis.

To elucidate the relationship between angiogenesis and prognosis after curative resection of hepatocellular carcinoma (HCC). An immunohistochemical study using anti-CD34 monoclonal antibody was carried out on surgical specimens from 78 HCC patients who had undergone curative resection; microvessel density (MVD) was counted and the overall survival and disease-free survival were analyzed retrospectively. Blood vessels in the tumor were strongly stained by anti-CD34 antibody, but not those in the surrounding liver parenchyma. There were three types of tumor vessels: capillary-like (n = 59), sinusoid-like (n = 16) and mixed-type (n = 3). The median MVD count was 100 per field. The HCC were designated as hypovascular (n = 36) with an MVD count below 100, and hypervascular (n = 42) with an MVD count of 100 or more per field. The 5-year survival and disease-free survival rates were 49.7% and 42.8% respectively, and statistical analysis showed that the MVD level was not correlated with tumor size, capsule status, Edmondson's grade, alpha-fetoprotein level, associated cirrhosis, gamma-glutamyltransferase, and serum HBsAg status. The sinusoid-like tumor vessels appeared more frequently in the more differentiated tumors (P<0.05). No statistical difference in overall and disease-free survival between different MVD levels and microvessel types was found. Tumor size was the only predicting factor in the entire series. In patients with small HCC (< or =5 cm, n = 40), 5-year survival and disease-free survival rates were 58.9% and 52.7% respectively, higher than the values in large HCC (39.8% and 32.0% respectively, P<0.05). The MVD level was an independent predicting factor of disease-free survival, 5-year disease-free survival in the hypovascular group (74.6%) being better than that in the hypervascular group (34.7%, P<0.05). The MVD level was not related to tumor size, capsule statuo, Edmondson's grade, alpha-fetoprotein level, associated cirrhosis, gamma-glutamyltransferase and serum HBsAg status. In the entire series, tumor size was the only factor influencing survival after curative resection. However, in patients with small HCC, the MVD level was an independent factor of disease-free survival. The pathological and clinical implications of different types of tumor vessels in HCC remain to be studied.

Prognostic significance of angiogenesis in human pancreatic cancer.

To evaluate whether angiogenic factors are of clinical relevance to actual human pancreatic cancers, we studied the intratumoral microvessel density (IMD), and PD-ECGF, VEGF protein expression in 40 pancreatic cancers using immunohistochemistry. We also investigated PD-ECGF and VEGF gene expression using reverse transcriptase-PCR (RT-PCR). Of the 40 pancreatic cancers studied, 30 carcinomas (75.0%) were evaluated to be PD-ECGF-positive and 10 carcinomas (25.0%) were determined to be PD-ECGF-negative. In contrast, 27 carcinomas (67.5%) were evaluated to be VEGF-positive, whereas 13 carcinomas (32.5%) were VEGF-negative. VEGF gene expression was moderately associated with an increase in the IMD (r2 = 0.181, P = 0.006), but no significant relationship was found between PD-ECGF gene expression and the IMD (r2 = 0.093, P = 0.059). However, tumours with positive expression for both PD-ECGF and VEGF had a higher IMD (P = 0.027). The results of the immunohistochemistry agreed well with the results of the quantitative RT-PCR. The median survival time of the hypervascular group was significantly shorter than that of the hypovascular group (P < 0.0001). In comparing the survival according to PD-ECGF and VEGF gene expression, the median survival time of the patients with positive PD-ECGF expression was significantly shorter than those with negative PD-ECGF expression (P = 0.040). Furthermore, the median survival time of the patients with positive VEGF expression was significantly shorter than those with negative VEGF expression (P = 0.048). However, the Cox multivariate analysis indicated that the IMD and VEGF expression were independent prognostic factors of the various clinicopathologic variables in pancreatic cancer patients (P = 0.0021 and P = 0.0443, respectively). © 1999 Cancer Research Campaign

Microvessel count predicts metastasis and prognosis in patients with gastric cancer.

In order to evaluate the clinical relevance of angiogenesis in patients with gastric cancer, we investigated the microvessel count in gastric cancer tissues and compared the results with several clinicopathologic factors and prognosis. A total of 55 patients with gastric cancer were included in this study. Microvessel count was determined by immunohistochemical staining using antifactor VIII-related antigen antibody. Histologically recognizable blood vessels within tissue sections served as internal control for immunostaining. Normal mouse IgG diluted to an equivalent protein concentration was used as a negative control in place of the primary antibody in each experiment. The microvessel count ranged from 4.4 to 39.8 and the median count was 15.6. Microvessel count was significantly higher in patients with hepatic metastasis, lymph node metastasis, adjacent organ invasion, and lymphatic invasion. In patients who had undergone a curative operation, survival time in the hypervascular group was significantly shorter than that in the hypovascular group. Microvessel count correlated well with tumor progression and may serve as a useful prognostic factor in patients with gastric cancer.

Selective Bronchial Arteriography and Hemoptysis in Nonmalignant Lung Disease

We consider that in the majority of cases, bloody sputum or hemoptysis in nonmalignant diseases is derived from the bronchial circulatory system. Selective bronchial arteriographic examination was performed in 122 patients with benign pulmonary diseases. In the markedly hypervascular group, the patients who had blood in sputum were significantly larger in number than those of moderate or mild groups. Bronchopulmonary anastomosis was found in 45 patients. Out of the 45 patients, 23 had blood in sputum or hemoptysis whereas 19 of the remaining 77 without anastomosis had this episode. The difference in frequency of blood in sputum or hemoptysis between these two groups with or without the anastomosis was statistically significant (P