Stroma AReactive Invasion Front Areas (SARIFA)—A New Easily to Determine Biomarker in Colon Cancer—Results of a Retrospective Study

Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor–stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p < 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (<1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers.

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Interobserver Variability in the Assessment of Tumor Budding in pT 3/4 Colon Cancer: Improvement by Supporting Immunohistochemistry?

Diagnostics ◽

10.3390/diagnostics10090730 ◽

2020 ◽

Vol 10 (9) ◽

pp. 730

Author(s):

Benedikt Martin ◽

Patrick Mayr ◽

Regina Ihringer ◽

Eva-Maria Schäfer ◽

Elżbieta Jakubowicz ◽

...

Keyword(s):

Colon Cancer ◽

Interobserver Variability ◽

Prognostic Significance ◽

Distant Metastases ◽

Consensus Conference ◽

Tumor Budding ◽

Cancer Specific Survival ◽

Cytokeratin Immunohistochemistry ◽

Different Levels ◽

Level Of Agreement

The prognostic significance of tumor budding in colon cancer is unequivocally documented, and the recommendations of the International Tumor Budding Consensus Conference (ITBCC) are currently the accepted basis for its assessment. Up to now, it is unknown whether the general use of a supporting cytokeratin immunohistochemistry can improve the interobserver variability and prognostic significance. Six investigators with different levels of experience reassessed 229 cases of colon carcinoma (pT3/4, N+/−, M0) with a supporting cytokeratin immunohistochemistry. The results were compared to previous assessments, which have been performed only on H & E. Bd3 was significantly associated with the occurrence of distant metastases according to the assessments of three out of six investigators (p < 0.05). Only one single investigator reached significant results concerning the cancer specific survival (p = 0.01). The pairwise kappa values range between a poor and moderate level of agreement (range 0.17–0.45; median 0.21). In conclusion, the results show no superiority of the use of an additional cytokeratin immunohistochemistry compared to the conventional analysis on sole H & E slides. Therefore, the general supporting use of a cytokeratin immunohistochemical staining seems to be inadvisable in colon cancer in consideration of necessary resources and costs.

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Systemic immune‐inflammation index has prognostic significance in pancreatic carcinoma patients: a meta-analysis

10.21203/rs.3.rs-117731/v2 ◽

2021 ◽

Author(s):

Xiaocheng Li ◽

Huapeng Lin ◽

Renbin Ouyang ◽

Yaowei Yang ◽

Jing Peng

Keyword(s):

Pancreatic Carcinoma ◽

Fixed Effects ◽

Meta Analysis ◽

Prognostic Significance ◽

Prognostic Indicator ◽

Cochrane Library ◽

Cancer Specific Survival ◽

Non Invasive ◽

Promising Tool ◽

Immune Inflammation

Abstract Background Systemic immune-inflammation index (SII) is reportedly a prognostic indicator for several malignancies, including pancreatic carcinoma, although there exists no consensus regarding its significance. In the current study, we used a systematically meta-analysis to evaluate the association between SII and prognosis in pancreatic carcinoma patients. Methods We screened PubMed, Embase and Cochrane Library databases, through May 2020, and retrieved studies describing the prognostic role of SII in pancreatic carcinoma. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) using a random or fixed effects models to reveal the correlation between SII and prognosis. Results A total of 4 studies, comprising 1,749 patients, met our inclusion criteria and were therefore eligible for inclusion. Our meta-analysis showed that elevated SII indicated significantly worse overall survival in patients with pancreatic carcinoma (HR: 1.43, 95% CI: 1.24–1.65, P < 0.001), with subgroup analyses, stratified by the TNM stage and treatment, further validating these results. In addition, patients with high SII had poorer cancer-specific survival (HR: 2.32, 95% CI: 1.55–3.48, P < 0.001). However, we found no significant associations between SII with disease-free and relapse-free survival. Conclusions These findings indicate that SII is a potential non-invasive and promising tool for predicting clinical outcomes of pancreatic carcinoma patients. However, further studies using adequate designs and larger sample sizes are required to validate our findings.

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Prognostic Significance of Substance P/Neurokinin 1 Receptor and Its Association with Hormonal Receptors in Breast Carcinoma

BioMed Research International ◽

10.1155/2021/5577820 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Riffat Mehboob ◽

Syed Amir Gilani ◽

Amber Hassan ◽

Sadaf ◽

Imrana Tanvir ◽

...

Keyword(s):

Breast Carcinoma ◽

Substance P ◽

Tumor Cells ◽

Prognostic Significance ◽

Positive Staining ◽

Ki 67 ◽

Neurokinin 1 Receptor ◽

Group A ◽

Neurokinin 1 ◽

Group B

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as “+3,” was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as “+2” (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining “+1” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.

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Antiplatelet Agents as Secondary Thromboprophylaxis after Anticoagulant Treatment for Thrombosis.

Blood ◽

10.1182/blood.v108.11.4127.4127 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4127-4127

Author(s):

Georgia Papaioannou ◽

Emmanouil Papadakis ◽

Maria Topalidou ◽

Kyriaki Kokoviadou ◽

Anastasia Karapiperidou ◽

...

Keyword(s):

Antiplatelet Agent ◽

Prognostic Significance ◽

Antiplatelet Agents ◽

Recurrence Risk ◽

Late Recurrence ◽

Venous Thromboembolic Event ◽

Low Dose Aspirin ◽

Venous Thromboembolic ◽

Group A ◽

Group B

Abstract Patients suffering an unprovoked VTE event have high risk of recurrence after anticoagulation cessation especially in the first two-year period. Our study examined whether secondary thromboprophylaxis with antiplatelet drugs reduces the relapse risk. STUDY DESIGN: We studied 53 patients, 25 men and 28 women, (group A), with median age of 41(18–74) years. 31 received aspirin at 100mg while 22 received clopidogrel at 75mg after anticoagulant therapy for VTE. We compared them with 77 patients (group B) who did not receive any thromboprophylaxis after VTE with a median age of 40(18–82) years. Of group B, 56 were men while 21 were women. In 51 out of 130 patients we monitored D-dimers, F1+2 prothrombin fragments, and TAT (thrombin-antithrombin) complexes as prothrombotic and fibrinolysis markers. Failure was determined as VTE recurrence or elevation of prothrombotic markers in the first 2year period. RESULTS: In 4 patients of group A (7,5%) we noticed marked elevation of prothrombotic markers and they were turned to anticoagulation, and in 3 marker elevation subsided by changing the antiplatelet agent (aspirin to clopidogrel). 1 patient stopped prophylaxis due to hemorrhage while none relapsed. In group B VTE recurrence was noticed at 27(36%, p<0,0002). In both groups late recurrence (> 2 years) was observed at 27,6% of 130 patients. CONCLUSIONS: Low dose aspirin or clopidogrel administration is safe and effective as thromboprophylaxis after anticoagulation for first venous thromboembolic event. Markers as D-dimers, F1+2, TAT, have prognostic significance and are valuable tools in patient monitoring. Patient follow-up has to be long-standing because VTE recurrence risk persists through the years.

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A pilot study of the immunohistochemical pattern of neuropilin-2 (NRP2) labeling and correlation with tumor stage in colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14098 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14098-e14098

Author(s):

Hongliu Sun ◽

Ashleigh M. Kussman ◽

Carol Freeman ◽

Judy Meredith ◽

Kenneth Hensley ◽

...

Keyword(s):

Colon Cancer ◽

Pilot Study ◽

Internal Control ◽

Medical Center ◽

Tumor Grade ◽

Prognostic Indicator ◽

Tumor Stage ◽

Cancer Tissue ◽

Cytoplasmic Staining ◽

Tissue Sections

e14098 Background: Neuropilin 2 (NRP2) is a transmembrane glycoprotein, non-associated with kinase domains, implicated in neovascularization and metastasis of colon cancer. NRP2 has been proposed as a molecular marker for targeted cancer therapy based on its multiple functions in cancer promotion. NRP2 signaling pathway and its expression have been demonstrated in many carcinomas. To the best of our knowledge, no description of the immunohistochemical staining pattern of NRP2 in colon cancer has been published in the English medical literature. The aim of this study is to investigate the NRP2 labelilng pattern in colon cancer and correlate it with tumor stage. Methods: Tumor sections from 35 randomly selected colectomy specimens with colorectal cancer collected during the last three years were retrieved from the University of Toledo Medical Center Department of Pathology archival material. Formalin fixed, paraffin embedded, 4 μm tissue sections containing invasive tumor were immunolabeled with a commercial antibody against NRP2, using a Ventana Benchmark LT automated instrument. Randomized, immunolabeled colon cancer tissue sections were blindly reviewed by two pathologists. Cytoplasmic and nuclear expression of NRP2 by tumor cells was graded as negative (no staining), focal (staining in <50% of cells), and diffuse (staining in ≥ 50% of cells). Adjacent benign colonic mucosa was used as an internal control. Results: No T1 or T2 tumor displayed diffuse nuclear labeling for the NRP2 epitope. In contrast, 13/20 T3 tumors (65%) and 4/4 T4 tumors (100%) displayed diffuse nuclear labeling. The association of diffuse nuclear NRP2 labeling with tumor grade was highly statistically significant (p=0.0055 by Chi-squared test). In contrast to nuclear labeling, cytoplasmic staining was observed in all stages and varied from negative to diffuse, but demonstrated no significant correlation with stage. Conclusions: This pilot study on colon cancer specimens suggests that diffuse nuclear immunolabeling of neuropilin-2 is indicative of a higher tumor stage. This finding suggests a potential use for this marker as a prognostic indicator for colon cancer in small biopsy samples.

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Clinical impact of D3 lymph node dissection preserving left colic artery (LCA) compared to D3 without preserving LCA: Exploratory subgroup analysis of data from randomized controlled trial of laparoscopic versus open surgery for colon cancer from Japan Clinical Oncology Group study JCOG0404.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.653 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 653-653

Author(s):

Tomonori Akagi ◽

Takao Hara ◽

Masafumi Inomata ◽

Junki Mizusawa ◽

Hiroshi Katayama ◽

...

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Lymph Node Dissection ◽

Controlled Trial ◽

Node Dissection ◽

Intestinal Paralysis ◽

Group A ◽

Group B ◽

Lca Group ◽

D3 Lymph Node Dissection

653 Background: In curative resection of sigmoid colon and rectal cancer, it is unclear whether D3 lymph node dissection preserving left colic artery (LCA) (Group A) is beneficial compared to D3 without preserving LCA (Group B) in terms of clinical outcomes. Preservation of LCA is expected to maintain blood supply which results in preventing anastomotic leakage, intestinal paralysis, and so on. Methods: The data of JCOG0404 (which is a randomized controlled trial comparing open to laparoscopic surgery for stage II/III colon cancer) were used. Eligibility criteria in JCOG0404 included histologically proven colon cancer; T3 or deeper lesion without involvement of other organs; N0-2 and M0. D3 lymph node dissection with or without preserving LCA was identified according to the photographs of the resected field collected for central surgical review in JCOG0404. The short and long-term outcomes were compared between each procedure. Results: Among all randomized 1057 patients in JCOG0404, 631 patients who received assigned sigmoid colectomy and anterior resection were included in the subgroup analysis. The number of patients were 135 in Group A and 496 in Group B. The patient backgrounds did not differ between groups. The median operative time, median blood loss, and the proportion of grade 1 or more anastomotic leakage and intestinal paralysis were not remarkably different (Group A vs. Group B: 185 min vs 186 min, 60 ml vs. 50 ml, 3.0% vs. 5.0%, and 2.2% vs. 3.8%). However, overall postoperative complication occurred more in Group B than in Group A (9.6% and 21.6%, p = 0.022). In terms of efficacy, 5-year relapse-free survival (RFS) and overall survival (OS) tended to be better in Group A than Group B (RFS: 83.7% and 80.5%, HR 1.25 (95% CI 0.79-1.96), OS: 96.3% and 91.1%, HR 2.47 (95% CI 1.13-5.40)). Conclusions: Short and long-term outcomes were better in Group A than Group B. It was considered that D3 lymph node dissection preserving LCA could be alternative treatment for D3 lymph node dissection. Clinical trial information: C000000105.

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Clinical study on the tunnel approach in laparoscopic radical right hemicolectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16135 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16135-e16135

Author(s):

Xijie Zhang ◽

Junli Zhang ◽

Yuzhou Zhao

Keyword(s):

Colon Cancer ◽

Operation Time ◽

Right Hemicolectomy ◽

Lateral Approach ◽

Radical Right ◽

Lymph Node Yield ◽

Group A ◽

Laparoscopic Right Hemicolectomy ◽

Group B ◽

Approach Group

e16135 Background: The medial to lateral approach Laparoscopic right hemicolectomy complies with the “no-touch” principle, but need a demanding procedure with a steep learning curve. This study was designed to assess the superiority of the tunnel approach compared to traditional medial-to-lateral approach in laparoscopic right hemicolectomy for patients with right-sided colon cancer. Methods: The new method was called Tunnel Approach: The tunnel was formed with Toldt's gap was dissociated upward from the attachment of ileocecal part and retroperitoneum, then the right mesocolon was lifted to expose and divide the superior mesenteric blood vessel. We analyzed retrospectively the patients with resectable right-sided colon cancer confirmed by colonoscope and imaging who received the laparoscopic radical right hemicolectomy. The patients were divided into the tunnel approach (group A) and the traditional medial-to-lateral approach (group B) according to the surgical maneuver performed. Results: A total of 84 patients who received laparoscopic radical right hemicolectomy were assigned to group A (n = 42) or group B (n = 42) between January 2016 to June 2017. There was no difference in baseline characteristics including demographics, body mass index (BMI), tumor stage, tumor location and differentiation. The operation time and intraoperative blood loss in group A were significantly better than group B (137.74±22.7 vs. 153.1±28.8min, p < 0.05; 49.0±40.7 vs. 142.9±87.4ml, p < 0.05, respectively).There was no difference in tumor size(5.7±2.1 vs. 5.7±2.1cm, p>0.05), conversion to laparotomy rate(0 vs. 3, p>0.05), lymph node yield(30.5±14.4 vs. 27.9±12.7, p>0.05), time to first flatus(3.4±1.3 vs. 4.0±1.3d, p>0.05), postoperative hospital stays(10.0±2.2 vs. 12.3±3.0d, p>0.05) and complications(2 vs. 3, p>0.05) between two groups. There was no treatment-related death in both groups. Conclusions: The characteristic of “tunnel” approach is to convert the anatomy from a two-dimensional to a three-dimensional view, it showed the benefits of both speed and safety with low intraoperative conversion to laparotomy rate and mortality. This new tunnel approach right hemicolectomy is worth recommended.

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Prognostic Significance of Peritumoral Edema in Patients With Vestibular Schwannomas

Neurosurgery ◽

10.1227/neu.0000000000000748 ◽

2015 ◽

Vol 77 (1) ◽

pp. 81-86 ◽

Cited By ~ 3

Author(s):

Madjid Samii ◽

Mario Giordano ◽

Hussam Metwali ◽

Osamah Almarzooq ◽

Amir Samii ◽

...

Keyword(s):

Prognostic Significance ◽

Magnetic Resonance Images ◽

Vestibular Schwannomas ◽

Peritumoral Edema ◽

Tumor Bed ◽

Fluid Attenuated Inversion Recovery ◽

Group A ◽

Group B ◽

Skull Base Meningiomas

Abstract BACKGROUND: Peritumoral edema (PTE) in skull base meningiomas correlates to the absence of an arachnoid plane and difference in outcome. In vestibular schwannomas (VS), PTE and its significance for microsurgery and outcome have never been systematically evaluated. OBJECTIVE: To evaluate whether PTE correlates with tumor characteristics, the presence of an arachnoid plane, and outcome. METHODS: A retrospective study of the institutional database. PTE was evaluated on fluid-attenuated inversion recovery magnetic resonance images. Preoperative patient data and intraoperative tumor features (presence of tumor pseudocapsule, vascularity, degree of adhesion/invasion of the arachnoid) were noted. Outcome measures were completeness of removal, neurological outcome, and complication rate. These parameters in patients with PTE (group A) were correlated to those in matched series without edema (group B). RESULTS: Thirty patients presented with PTE (5%). The mean VS size was 3.4 cm. No major differences in the degree of adhesion or presence of an arachnoid plane were found. VS with PTE were more frequently hypervascular (26.7% in group A vs 6.7% in group B). The presence of PTE in VS was not related to surgical radicality. VS with PTE had worse early postoperative facial nerve function, but at 12 months, there was no major difference. VS with PTE were prone to cause postoperative hemorrhages in the tumor bed. CONCLUSION: PTE in VS does not correlate with the degree of tumor adhesion and the presence of an arachnoid dissection plane. The radicality of tumor removal and long-term functional outcome in patients with and without PTE was similar. VS with PTE are more vascular and prone to cause postoperative hemorrhages. Therefore, meticulous hemostasis is advisable.

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Prognostic value of non-ischemic ring-like left ventricular scar pattern in patients with apparently idiopathic ventricular arrhythmias: a CMR imaging study

European Heart Journal ◽

10.1093/ehjci/ehaa946.0207 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

G Nucifora ◽

D Muser ◽

S Castro ◽

R Casado Arroyo ◽

D Benhayon ◽

...

Keyword(s):

Ventricular Arrhythmias ◽

Prognostic Significance ◽

Imaging Study ◽

Left Ventricular ◽

High Rate ◽

Life Threatening ◽

History Of ◽

Group A ◽

Group B

Abstract Background The presence of left ventricular (LV) late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has been correlated to life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). Aim of the present study was to investigate the prognostic significance of a specific LV-LGE phenotype characterized by a subepicardial/midmyocardial “ring-like” pattern of fibrosis. Methods Out of a total of 518 consecutive patients with apparently idiopathic VAs who underwent CMR study, 79 (15%) had evidence of LV-LGE. Of these, 23 (4%) patients had LV LGE with ring-like pattern, defined as subepicardial or midmyocardial LGE involving at least 3 contiguous segments in the same slice (group A), while 56 (11%) patients had LV LGE with no ring-like pattern (group B). The remaining 439 patients had no LGE (group C). The end-point of the study was a composite SCD, resuscitated cardiac arrest and nonfatal episodes of ventricular fibrillation or documented sustained ventricular tachycardia. Results Group A patients were more frequently males compared to groups B and C (96% vs. 79% vs. 52%; p<0.01) and had more frequently a family history of SCD and/or cardiomyopathy (30% vs. 11% vs. 5%; p<0.01). All patients in Group A showed VAs with a predominant RBBB morphology vs. 38 (68%) patients in Group B and 65 (15%) in Group C (p<0.01). During a follow-up of 63±39 months, the composite outcome occurred in 13 patients (57%) in Group A vs. 11 (20%) in Group B and 2 (1%) in Group C (p<0.01). Conclusion In patients with apparently idiopathic VAs, a nonischemic LV-LGE with a ring-like pattern at CMR is associated with a high rate of malignant arrhythmic events during follow-up. Funding Acknowledgement Type of funding source: None

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The effect of different doses of bevacizumab and irinotecan on tumor growth of nude mice bearing human colon cancer DLD-1.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.518 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 518-518

Author(s):

Luo Cong

Keyword(s):

Colon Cancer ◽

Tumor Growth ◽

Nude Mice ◽

Tumor Angiogenesis ◽

Human Colon ◽

Control Group ◽

Human Colon Cancer ◽

Group A ◽

Group B ◽

Different Doses

518 Background: Anti-angiogenic therapy is an important therapeutic strategy in advanced colorectal cancer. However, the anti-angiogenic drug,such as bevacizumab(avastin) is expensive. So, clarifying whether different doses of avastin play the same effect in vivo is urgently needed. The aim of the study was to observe the different doses of avastin in combination with irinotecan in human colon tumor growth in nude mice and tumor angiogenesis. Methods: 21 nude mice inoculated with DLD-1 human colon cancer cells were randomly divided into four groups: sterile saline control (group A), 5mg/kg avastin plus irinotecan chemotherapy group (group B), 10mg/kg avastin plus irinotecan group (group C), and irinotecan chemotherapy group (group D). Drugs were administered in the first 1,5,9 days, mice were sacrificed in the 10th day after treatment, the tumor growth inhibitory rate was calculated and the tumor microvessel density (MVD) were detected by immunohistochemistry. Results: The tumor inhibition rate in groups B, C, and D were 62.85%, 47.91%, 39.59% respectively. A, B, C, and D groups’ MVD were 7.000 ± 0.71, 4.940 ± 0.58, 5.080 ± 1.25, 5.557 ± 2.04, The MVD in group B and C were significant different compared with group A by Dunnett's test, and the MVD expression difference between D, A groups and B, C groups did not reach statistical significance (P values were 0.086,0.083). Tissue necrosis was found in each group after HE staining of tumor tissue. Among them, the control group, mostly mild to moderate necrosis, and the necrosis area were increased after drug treatment. But there were no statistical differences of the necrotic area in drug treated groups graded by rank sum test (χ2 = 4.73, P = 0.193). And cell apoptosis was obviously seen in treated groups. Conclusions: Different doses of avastin with irinotecan inhibited the tumor growth on DLD-1 xenografted nude mice, Synergistic effects were observed in combination therapy, From cell morphology changes after staining with HE, we speculated that the mechanism may be related to the inhibition of tumor angiogenesis, and cell apoptosis increasing. The effect of 5mg/kg and 10mg/kg bevacizumab on tumor volume and MVD had no significant differences.

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