Persistent Sciatic Artery and its role in limb salvage in oncological surgery.

AIM: The Persistent Sciatic Artery (PSA) is a rare congenital anomaly due to missed involution of embryo-fetal sciatic artery, which is the main blood supply to lower limb during embryonic development until superficial femoral artery (SFA) is formed. The PSA is frequently related to complications in adults like aneurysm and embolism. Here we present a case in which the discovery of a complete PSA resulted limb saving. In case of oncologic or trauma surgery, when no other options are available, the PSA can help in management of reconstructive surgery. CASE REPORT: A case of PSA was discovered during management of a patient affected by a soft tissue sarcoma of the lower limb. Tumor resection needed the femoral neurovascular bundle demolition to ensure radical surgery and subsequent vascular reconstruction, which failed due to complications. RESULTS: Despite failure reconstruction, a misdiagnosed type IIa PSA, replacing the role of the SFA, saved the lower limb from ischemia and subsequent amputation. Functional reconstruction was thus achieved with almost total recovery of lower limb function. DISCUSSION AND CONCLUSIONS: In oncological and trauma surgery we recommend investigate the whole lower limb vascularization, from the pelvis to the foot, suspecting the PSA existence. Indeed, although it is always preferable to reconstruct the SFA system despite a complete PSA is present, due to its frequent complications, the PSA can represent a limb saving option. KEY WORDS: Computerized tomography angiography, Persistent sciatic artery, PSA, Superficial femoral artery, SFA fibromyxoid sarcoma.

Multiparametric quantitative analysis of tumor perfusion and diffusion with 3T MRI: differentiation between benign and malignant soft tissue tumors.

OBJECTIVE: To evaluate multiparametric MRI for differentiating benign and malignant soft tissue tumors. METHODS: This retrospective study included 67 patients (mean age, 55 years; 18-82 years) with 35 benign and 32 malignant soft tissue tumors. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI)-derived parameters (D, D*, f), apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE)-MRI parameters (Ktrans, Kep, Ve, iAUC) were calculated. Myxoid and non-myxoid soft tissue tumors were divided for subgroup analysis. The parameters were compared between benign and malignant tumors. RESULTS: ADC and D were significantly lower in malignant than benign soft tissue tumors (1170 ± 488 vs 1472 ± 349 µm2/s; 1132 ± 500 vs 1415 ± 374 µm2/s; p < 0.05). Ktrans, Kep, Ve, and iAUC were significantly different between malignant and benign soft tissue tumors (0.209 ± 0.160 vs 0.092 ± 0.067 min-1; 0.737 ± 0.488 vs 0.311 ± 0.230 min-1; 0.32 ± 0.17 vs 0.44 ± 0.28; 0.23 ± 0.14 vs 0.12 ± 0.09, p < 0.05, respectively). ADC (0.752), D (0.742), and Kep (0.817) had high AUCs. Subgroup analysis showed that only Ktrans, and iAUC were significantly different in myxoid tumors, while, ADC, D, Ktrans, Kep, and iAUC were significantly different in non-myxoid tumor for differentiating benign and malignant tumors. D, Kep, and iAUC were the most significant parameters predicting malignant soft tissue tumors. CONCLUSION: Multiparametric MRI can be useful to differentiate benign and malignant soft tissue tumors using IVIM-DWI and DCE-MRI. ADVANCES IN KNOWLEDGE: 1. Pure tissue diffusion (D), transfer constant (Ktrans), rate constant (Kep), and initial area under time-signal intensity curve (iAUC) can be used to differentiate benign malignant soft tissue tumors.2. Ktrans and iAUC enable differentiation of benign and malignant myxoid soft tissue tumors.

Novel therapeutic options for alveolar soft part sarcoma: antiangiogenic therapy, immunotherapy and beyond.

PURPOSE OF REVIEW: Alveolar soft part sarcoma (ASPS) represent 0.5% of sarcomas, defining a rarest among rare malignancies. It affects young adults, displaying slow-growing mass of the thigh, head and neck, and trunk. Although quite indolent, a majority of cases displays an advanced disease with lung bone or central nervous system metastasis. Complete surgery is the cornerstone of localized ASPS, and advanced diseases poorly respond to chemotherapy. Here discuss recent progress in molecular characterization of ASPS and future prospects of therapeutic approaches. RECENT FINDINGS: ASPS is characterized by a specific oncogenic translocation ASPSCR1-TFE3 that induce hepatocyte growth factor receptor (MET) overexpression, angiogenesis, and immunosuppression in the tumor microenvironment. These specific biological features have encouraged the successful exploration of MET inhibitors, antiangiogenic drugs, and immunotherapy. We reviewed the main tracks of ASPS biology and recent insights from targeted therapies is ASPS mainly driven tyrosine kinase inhibitors (especially antiangiogenics), immune-checkpoint inhibitors, and their combinations. SUMMARY: Overall, antiangiogenics and anti Programmed cell death 1/Programmed cell death ligand 1 therapies showed a significant activity in ASPS that warrants additional investigation through randomized trials to validate those results and through ancillary biological studies to better understand resistance mechanisms and biomarkers of response.

Soft Tissue Lesions With High Vascular Density on Sonography in Pediatric Patients: Beyond Hemangiomas [Formula: see text].

Infantile hemangiomas are the most frequent vascular soft tissue lumps in the pediatric population. The clinical presentation and evolution of these lesions is characteristic, while the sonographic appearance is classic but not specific. This pictorial essay illustrates the different vascular soft tissue lumps on ultrasound that may mimic infantile hemangiomas. Awareness of these mimics is crucial to avoid misdiagnosis. Clinical and sonographic discriminators for each lesion are presented.

Feeding arteries and arteriovenous shunt for discrimination of soft tissue tumors.

Time resolved magnetic resonance angiography with interleaved stochastic trajectories (TWIST) allows for identification of tumor feeding arteries and arteriovenous shunt (AVS). We used TWIST to obtain number of feeding arteries (NFA) and detect AVS for 43 cases of pathology-confirmed soft tissue tumors. We compared normalized number of feeding arteries (nNFA) and AVS between malignant and benign tumors, and found nNFA was significantly greater in malignant tumors versus benign tumors (2.1 vs 1.3, P < .05). The incidence of AVS was significantly higher in malignant tumors versus benign tumors (87.5% vs 10.5%, P < .05). TWIST derived nNFA and AVS could be useful in the discrimination of benign and malignant soft tissue tumors.

[Angiofibroma of soft tissue: a clinicopathologic analysis of 24 cases].

Objective: To investigate the clinicopathologic and genetic features, pathologic diagnosis and differential diagnosis of angiofibroma of soft tissue(AFST). Methods: The clinicopathologic characteristics of 24 cases diagnosed at Fudan University Shanghai Cancer Center from 2011 to 2017 were analyzed; immunohistochemical staining and interphase fluorescence in situ hybridization (FISH) were performed, and the literatures were also reviewed. Results: There were 15 male and 9 female (male∶female=1.7∶1.0) patients with age of onset ranging from 8 to 68 years (mean, 45 years). Fourteen cases occurred in extremities, including upper limbs (n=3) and lower limbs (n=11); seven cases were in the trunk, and 1 case each was in the temporal region, retroperitoneum and liver, respectively. Clinically, the tumors usually presented as a slowly growing painless mass. Tumor sizes ranged from 0.8 to 14 cm (mean 4.6 cm). Microscopically, most lesions were well-circumscribed, with fibrous capsules. Few cases infiltrated the surrounding fibrofatty tissue focally. The tumors were mainly composed of sparse short spindle cells and numerous small, branching, thin-walled blood vessels distributed in amyxoid, fibromyxoid or collagenous matrix, often accompanied by medium-sized, round or irregular and ecstatic vessels at the tumor periphery.By immunohistochemistry, all tested cases expressed vimentin (5/5), and showed variable positivity for EMA (2/4), ER (1/2), PR (2/3), α-SMA (1/18)and desmin (1/10). Ki-67 proliferation index were all less than 5%. CD34, CD31 and ERG staining clearly outlined the contours of blood vessels in the stroma. Four cases were tested for NCOA2 gene rearrangement by FISH, of which three were positive. Follow-up data was available in 17 patients (range, 3 to 69 months; mean, 30 months) were all free of disease. Conclusions: Soft tissue angiofibroma is a benign fibroblastic neoplasm characterized by a prominent and complex vasculature set in a myxoid-to-collagenous stroma, and cytogenetically a distinctive NCOA2 gene rearrangement. Caution should be exercised for the possibility of potentially misinterpretation of AFST as vascular tumors and other myxoid soft tissue tumors.

Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX).

PURPOSE: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. METHODS: High-risk STS was defined as high-grade morphology (according to the Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size ≥8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. RESULTS: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. CONCLUSIONS: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.

Isolated limb perfusion for locally advanced angiosarcoma in extremities: A multi-centre study.

BACKGROUND: Angiosarcomas are rare and aggressive soft-tissue sarcomas. The only potential curative treatment is complete surgical excision. This study reports the outcome of isolated limb perfusion (ILP) with high-dose melphalan and tumour necrosis factor α for locally advanced angiosarcoma. MATERIAL AND METHODS: All patients who underwent an ILP for angiosarcomas between 1991 and 2016 in three tertiary referral centres were identified from prospectively maintained databases. RESULTS: A total of 39 patients were included, with a median follow-up of 18 months (interquartile range 6.1-60.8). Of these patients, 23 (58.9%) patients had a complete response (CR) after ILP, 10 (25.6%) had a partial response, 4 (10.3%) had stable disease and 2 (5.1%) patients had progressive disease immediately after ILP. A total of 22 patients developed local progression (56.4%), whereas nine (23.1%) developed distant metastases. The patients with CR had a significantly prolonged median local progression-free survival (PFS) (15.4 versus 7.3 months, p = 0.015) when compared with non-CR patients, and a trend towards better median overall survival (81.2 versus 14.5 months, p = 0.054). Six patients underwent multiple ILPs, whereby the CR rate of the first, second and third ILPs were 60%, 80% and 67%, respectively. Thirteen (33.3%) patients needed further surgical intervention, consisting of resection in eight patients (20.5%) and amputation in five patients (12.8%). CONCLUSION: ILP is an effective treatment option for patients with locally advanced angiosarcoma in the extremities, resulting in a high number of CRs, a high limb salvage rate and prolonged local PFS.

Magnetic Resonance Features and Characteristic Vascular Pattern of Alveolar Soft-Part Sarcoma.

OBJECTIVE: The aim of this study was to investigate the magnetic resonance (MR) features of alveolar soft-part sarcoma (ASPS). METHODS: We studied 12 patients with ASPS confirmed by pathology in this retrospective study. MR features were analyzed, especially for the location, morphology, signals, and related enhanced features of the tumor vessels. RESULTS: Flow voids were shown in the central part of the tumor on T2-weighted imaging (T2WI) in all patients; they were arrayed in a radiating mode gathered toward the center (8 cases), designated by us as vascular center-gathered syndrome (VCGS), or scattered like twigs (4 cases). The flow voids were accompanied by high signals in all patients, including tubular (6 cases) and platy (6 cases) signals. Slightly higher signals were shown in the peripheral part of the tumor in all patients. Flow voids in the peripheral part were shown in all patients, and the majority of the flow voids surrounded the tumor (8 cases). The vessels around the tumor in 9 patients showed high signals, and the majority of the vessels were located at the superior and inferior poles (8 cases). 6 patients underwent enhanced scanning, including moderate (5 cases) and significant enhancement (1 case). CONCLUSION: Low signals of radiating flow voids accompanied by high signals of slow blood flow or blood sinuses in the center part have high significance for the diagnosis of ASPS.

Frequent low-level mutations of protein kinase D2 in angiolipoma.

Tumours displaying differentiation towards normal fat constitute the most common subgroup of soft tissue neoplasms. A series of such tumours was investigated by whole-exome sequencing followed by targeted ultra-deep sequencing. Eighty per cent of angiolipomas, but not any other tumour type, displayed mutations in the protein kinase D2 (PRKD2) gene, typically in the part encoding the catalytic domain. The absence of other aberrations at the chromosome or RNA level suggests that PRKD2 mutations are critical for angiolipoma development. Consistently, the mutated PRKD2 alleles were present at low (3-15%) frequencies, indicating that only a subset of the tumour cells is affected. Indeed, by sequencing mature fat cells and other cells separately, the former typically showed the highest mutation frequencies. Thus, we hypothesize that altered PRKD2 signalling in the adipocytic cells drives tumourigenesis and, in agreement with its pivotal role in angiogenesis, induces the vessel formation that is characteristic for angiolipoma. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Preoperative transarterial embolization using gelatin sponge for hypervascular bone and soft tissue tumors in the pelvis or extremities.

BACKGROUND: Preoperative transcatheter arterial embolization for hypervascular bone and soft tissue tumors plays an important role in reducing intraoperative blood loss (IBL). PURPOSE: To evaluate the use of a gelatin sponge in preoperative transcatheter arterial embolization for hypervascular bone and soft tissue tumors in the pelvis or extremities. MATERIAL AND METHODS: Thirty-seven patients (21 men, 16 women; median age, 61 years; age range, 23-79 years) underwent preoperative transcatheter arterial embolization between April 2004 and January 2015. Medical records and images were reviewed, and the technical success rate, clinical success rate, and complications were evaluated. Technical success was defined as a devascularization rate of 75% or higher, and clinical success was defined as intraoperative blood loss (IBL) <1500 mL in cases undergoing surgery within 3 days of transarterial embolization and <3000 mL in cases operated 4 or more days later. RESULTS: Tumor sizes were in the range of 2.0-13.0 cm (median, 5.0 cm). The devascularization rate was decreased by >75% at follow-up angiography in all cases, and the technical success rate was 100 % (37/37). The median IBL was 491 mL (range, 30-3800 mL), and the clinical success rate was 89% (33/37). The minor complication of local pain was observed in 13 out of 37 cases (35%) during or after embolization, but was controllable by an analgesic. CONCLUSION: Preoperative transarterial embolization using a gelatin sponge appears to be feasible and safe, and may contribute to decreasing IBL.

Application of Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost Techniques to Prepare "Safe Margin" in the Rabbit VX2 Limb Tumor Model.

BACKGROUND: In this study, we aimed to establish the rabbit VX2 limb tumor model, and then prepare a "necrotic zone" as a safe margin by volumetric modulated arc therapy and simultaneous integrated boost (VMAT-SIB) technique applied in the areas where the tumor is located adjacent to the bone (GTVboost area). MATERIAL AND METHODS: Rabbits in the control group (n=10) were not treated, while those in the test group (n=10) were treated with the SIB schedule delivering a dose of 40Gy, 35Gy, 30Gy, and 25Gy to the GTVboost, GTV (gross tumor volume), CTV (clinical target volume), and PTV (planning target volume) in 10 fractions. Magnetic resonance diffusion-weighted imaging (MRDWI), 3-dimensional power Doppler angiography (3D-PDA), and histological changes were observed after radiotherapy. RESULTS: After radiotherapy, the two groups showed a significant difference in the GTVboost area. In the test group, the tumor necrosis showed a significantly low signal in DWI and high signal in apparent diffusion coefficient (ADC) maps. The 3D-PDA observation showed that tumor vascular structures decreased significantly. Histological analysis demonstrated that a necrotic zone could be generated in the GTVboost area, and microscopic examination observed cell necrosis and fibroplasia. CONCLUSIONS: This studies demonstrated the feasibility of using VMAT-SIB technique in the rabbit VX2 limb tumor model. The formation of a necrotic zone can be effectively defined as safe margin in the GTVboost area. showing potential clinical applicability.

Relationship of endothelial area with VEGF-A, COX-2, maspin, c-KIT, and DOG-1 immunoreactivity in liposarcomas versus non-lipomatous soft tissue tumors.

Soft tissue tumors are rare tumors that show a heterogeneous structure; thus far, their molecular behavior has not been elucidated. The aim of our study was to define the relationship between microvessel density (MVD), evaluated with CD31, and other immunohistochemical markers, such as vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), CD34, maspin, DOG-1, and c-KIT. Immunostains were done in 55 cases consisting of benign and malignant tumors, such as liposarcomas, dermatofibrosarcomas, and tumors with histiocytic differentiation. Renal tubes were used as external control for VEGF, maspin, and DOG-1. Although DOG-1 is considered a specific marker for gastrointestinal tumors (GISTs), its positivity, correlated with c-KIT and VEGF immunoexpression, was also shown by dermatofibrosarcomas and tumors with histiocytic and lipomatous differentiation, suggesting its possible pro-angiogenic role. Maspin expression was observed in adipose tissue tumors only. Regarding angiogenesis, 31 of the 55 cases were VEGF-positive, such positivity being directly correlated with COX-2 and CD34 positivity as evaluated in the tumor cells and also with MVD. Although no significant differences in angiogenic activity were found between benign and malignant non-lipomatous tumors, the MVD was directly correlated with the histological type/grade of liposarcomas. Based on these aspects, we conclude that VEGF/COX-2-induced angiogenesis is specific for non-lipomatous tumors, whereas liposarcomas are dependent on the VEGF/maspin angiogenic pathway. The DOG-1/c-KIT/VEGF target may be used for further personalized therapy of soft tissue sarcomas. No data about DOG-1 and maspin positivity in liposarcomas have been published to date.

Propeller flap reconstruction of abdominal defects: review of the literature and case report.

The abdominal wall is perfused anteriorly by the superior and deep epigastric vessels with a smaller contribution from the superficial system. The lateral abdominal wall is perfused predominantly from perforators arising from the intercostal vessels. Reconstruction of soft tissue defects involving the abdomen presents a difficult challenge for reconstructive surgeons. Pedicle perforator propeller flaps can be used to reconstruct defects of the abdomen, and here we present a thorough review of the literature as well as a case illustrating the perforasome propeller flap concept. A patient underwent resection for dermatofibrosarcoma protuberans resulting in a large defect of the epigastric soft tissue. A propeller flap was designed based on a perforator arising from the superior deep epigastric vessels and was rotated 90° into the defect allowing primary closure of the donor site. The patient healed uneventfully and was without recurrent disease 37 months following reconstruction. Perforator propeller flaps can be used successfully in reconstruction of abdominal defects and should be incorporated into the armamentarium of reconstructive microsurgeons already facile with perforator dissections.

Contrast-enhanced color Doppler ultrasonography increases diagnostic accuracy for soft tissue tumors.

Resolution of ultrasonography (US) has undergone marked development. Additionally, a new-generation contrast medium (Sonazoid) used for US is newly available. Contrast-enhanced US has been widely used for evaluating several types of cancer. In the present study, we evaluated the ability of color Doppler US (CDUS) and Sonazoid to differentiate between benign and malignant soft tissue tumors. A total of 180 patients (87 male, 93 female) were enrolled in the present study. The patient ages ranged from 1 to 91 years (mean 58.1±20.0 years). The maximum size, depth, tumor margins, shape, echogenicity and textural pattern were measured on gray-scale images. CDUS was used to evaluate the intratumoral blood flow with and without Sonazoid. Peak systolic flow velocity (Vp), mean flow velocity (Vm), resistivity index (RI) and pulsatility index (PI) of each detected intratumoral artery were automatically calculated with power Doppler US (PDUS). The present study included 118 benign and 62 malignant tumors. Statistical significances were found in size, depth, tumor margin and textural pattern but not in shape or echogenicity on gray-scale images. Before Sonazoid injection, CDUS findings showed 55% sensitivity, 77% specificity and 69% accuracy, whereas contrast-enhanced CDUS showed 87% sensitivity, 68% specificity and 74% accuracy. There were no statistically significant differences between malignant and benign tumors regarding the mean Vp, Vm, RI and PI values determined on PDUS. In conclusion, contrast-enhanced CDUS proved to be a reliable diagnostic tool for detecting malignant potential in soft tissue tumors.

G-protein-coupled receptor-2-interacting protein-1 is required for endothelial cell directional migration and tumor angiogenesis via cortactin-dependent lamellipodia formation.

OBJECTIVE: Recent evidence suggests G-protein-coupled receptor-2-interacting protein-1 (GIT1) overexpression in several human metastatic tumors, including breast, lung, and prostate. Tumor metastasis is associated with an increase in angiogenesis. We have showed previously that GIT1 is required for postnatal angiogenesis during lung development. However, the functional role of GIT1 in pathological angiogenesis during tumor growth is unknown. APPROACH AND RESULTS: In the present study, we show inhibition of angiogenesis in matrigel implants as well as reduced tumor angiogenesis and melanoma tumor growth in GIT1-knockout mice. We demonstrate that this is a result of impaired directional migration of GIT1-depleted endothelial cells toward a vascular endothelial growth factor gradient. Cortactin-mediated lamellipodia formation in the leading edge is critical for directional migration. We observed a significant reduction in cortactin localization and lamellipodia formation in the leading edge of GIT1-depleted endothelial cells. We specifically identified that the Spa homology domain (aa 250-420) of GIT1 is required for GIT1-cortactin complex localization to the leading edge. The mechanisms involved extracellular signal-regulated kinases 1 and 2-mediated Cortactin-S405 phosphorylation and activation of Rac1/Cdc42. Finally, using gain of function studies, we show that a constitutively active mutant of cortactin restored directional migration of GIT1-depleted cells. CONCLUSION: Our data demonstrated that a GIT1-cortactin association through GIT1-Spa homology domain is required for cortactin localization to the leading edge and is essential for endothelial cell directional migration and tumor angiogenesis.

Novel tubulin antagonist pretubulysin displays antivascular properties in vitro and in vivo.

OBJECTIVE: Pretubulysin (PT) is a novel, synthetically accessible myxobacterial compound that acts as a tubulin-depolymerizing agent and inhibits cancer cell growth in vitro and in vivo. Moreover, PT was found to attenuate tumor angiogenesis. Here, we hypothesized that PT could exert antivascular activities on existing tumor vessels. APPROACH AND RESULTS: We aimed to characterize the antivascular effects of PT and to elucidate the underlying mechanisms in endothelial cells. In vitro, PT rapidly induced endothelial hyperpermeability and a concentration-dependent disassembly of established endothelial tubes on Matrigel and in an ex vivo aortic ring model. It disrupted endothelial cell junctions and triggered F-actin stress fiber formation and cell contraction by the RhoA/Rho-associated protein kinase pathway without causing cell death. In vivo, using a hamster dorsal skinfold chamber preparation, PT significantly decreased blood flow and vessel diameter in hamster A-Mel-3 amelanotic melanoma tumors but not in the neighboring healthy tissue. In a second tumor model using mice with subcutaneous murine B16 melanoma tumors, a single dose of PT (10 mg/kg) caused a shut down of tumor blood flow and a strong central tumor cell necrosis within 24 hours. Repeated PT administration significantly decelerates tumor growth and seems to be well tolerated. CONCLUSIONS: In summary, we could show for the first time that the antitumor effect of PT is, at least in part, mediated via its antivascular activities on existing tumor vessels.

[Feasibility of volume perfusion CT (VPCT) imaging in antiangiogenic treatment of rabbit VX2 soft-tissue tumor].

OBJECTIVE: To explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of rabbit VX2 soft-tissue tumor to antiangiogenic treatment. METHODS: To establish an experimental animal model of VX2 soft tissue tumor on 20 New Zealand white rabbits. Twenty rabbits were randomly divided into 2 groups. The therapy group was treated with recombinant human endostatin (3 mg·kg⁻¹·d⁻¹) for 7 days, and the control group received saline in the same dose only. Four times of CT volume perfusion scan were performed before treatment and on the second, forth, seventh days of treatment, respectively. The value of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PMB) in the VX2 tumors were measured after scanning. The microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumors were determined using immunohistochemical staining. RESULTS: The tumor volume of the therapy group was (1.36 ± 0.73) cm³ on the forth day of treatment and (1.69 ± 0.68) cm³ on the seventh day of the treatment. The tumor volume of the control group was (2.35 ± 0.62) cm³ on the fourth day of treatment and (3.87 ± 0.93) cm³ on the seventh day of the treatment (P < 0.05). On the seventh day of treatment, tumor necrosis ratio of the therapy group and the control group was (25.58 ± 5.51)% and (42.93 ± 4.34)%, respectively (P < 0.05). Comparing the perfusion parameters between the two groups on the same day, and the second, forth, seventh days of treatment, the value of PMB of the therapy group was (70.36 ± 23.46) ml·100 ml⁻¹·min⁻¹, (79.64 ± 13.68) ml·100 ml⁻¹·min⁻¹ and (84.76 ± 3.55) ml·100 ml⁻¹·min⁻¹, respectively, and that in the control group was (26.61 ± 6.47) ml·100 ml⁻¹·min⁻¹, (33.74 ± 16.47) ml·100 ml⁻¹·min⁻¹ and (30.47 ± 10.64) ml·100 ml⁻¹·min⁻¹, respectively (P < 0.05). The value of BF in the therapy group and control group was (71.19 ± 12.21) ml·100 ml⁻¹·min⁻¹ and (43.56 ± 12.21) ml·100 ml⁻¹·min⁻¹, respectively, on the seventh day of treatment (P < 0.05). The parameters on different days in the same group were compared. In the control group, the value of BF on the seventh day of treatment was significantly lower than that before and on the second and forth days of treatment (P < 0.05). However, in the therapy group, the value of PMB on the second, forth, and seventh days of treatment was significantly higher than that before treatment (P < 0.05). MVD of tumor in the control group was increased gradually, whereas increased on the first day and then decreased more in the therapy group. The VEGF expressions did not differ significantly between the experimental and control groups. CONCLUSIONS: Volume perfusion CT is helpful to quantify the tumor perfusion and evaluate the functional changes of tumor vasculature, and then evaluate the early therapeutic effect of antiangiogenic treatment.