Vascularized Bone Graft Reconstruction Following Bone Tumor Resection at a Multidisciplinary Sarcoma Center: Outcome Analysis.

BACKGROUND/AIM: Limb-sparing procedures are frequently applied to improve patient outcomes. The use of vascularized bone grafts is associated with significant improvements in oncologic safety and functional satisfaction. This study highlights the clinical outcomes following tumor resection combined with vascularized bone graft reconstructions. PATIENTS AND METHODS: Twenty-five free vascularized bone grafts (17 fibulas, 5 iliac crests, 3 medial femoral condyles) were assessed with respect to consolidation and hypertrophy, functional and oncologic outcomes, and local complications. RESULTS: The rate of healing of fibular grafts after a median of 5 months was 86%. The rate of achieved unions of iliac crest grafts after a median of 5 months was 80%. In medial femoral condyle bone grafts, union occurred after a median of 4 months. Significant hypertrophy was observed in 13 patients. We identified six complications with highest rates in the fibula-group. Despite the high complications, functional results were highly satisfactory. CONCLUSION: Vascularized bone grafts represent a reconstructive approach, maintaining long-term functionality and cosmetic satisfaction without compromising tumor recurrence outcomes.

Lysosome purinergic receptor P2X4 regulates neoangiogenesis induced by microvesicles from sarcoma patients.

The tumor microenvironment modulates cancer growth. Extracellular vesicles (EVs) have been identified as key mediators of intercellular communication, but their role in tumor growth is largely unexplored. Here, we demonstrate that EVs from sarcoma patients promote neoangiogenesis via a purinergic X receptor 4 (P2XR4) -dependent mechanism in vitro and in vivo. Using a proteomic approach, we analyzed the protein content of plasma EVs and identified critical activated pathways in human umbilical vein endothelial cells (HUVECs) and human progenitor hematopoietic cells (CD34+). We then showed that vessel formation was due to rapid mitochondrial activation, intracellular Ca2+ mobilization, increased extracellular ATP, and trafficking of the lysosomal P2XR4 to the cell membrane, which is required for cell motility and formation of stable branching vascular networks. Cell membrane translocation of P2XR4 was induced by proteins and chemokines contained in EVs (e.g. Del-1 and SDF-1). Del-1 was found expressed in many EVs from sarcoma tumors and several tumor types. P2XR4 blockade reduced EVs-induced vessels in angioreactors, as well as intratumor vascularization in mouse xenografts. Together, these findings identify P2XR4 as a key mediator of EVs-induced tumor angiogenesis via a signaling mediated by mitochondria-lysosome-sensing response in endothelial cells, and indicate a novel target for therapeutic interventions.

Eribulin induces tumor vascular remodeling through intussusceptive angiogenesis in a sarcoma xenograft model.

Eribulin is a novel microtubule inhibitor that, similar to other types of microtubule inhibitors, induces apoptosis by inhibiting the mitotic division of cells. Besides this direct effect on tumor cells, previous studies have shown that eribulin has the potential to induce tumor vascular remodeling in several different cancers; however, the mechanisms underlying this phenomenon remain unclear. In the present study, we aimed to elucidate whether eribulin is effective against synovial sarcoma, a relatively rare sarcoma that often affects adolescents and young adults, and to histologically investigate the microstructure of tumor vessels after the administration of eribulin. We found that eribulin exhibits potent antitumor activity against synovial sarcoma in a tumor xenograft model and that tumor vessels frequently have intervascular pillars, a hallmark of intussusceptive angiogenesis (IA), after the administration of eribulin. IA is a distinct form of angiogenesis that is involved in normal developmental processes as well as pathological conditions. Our data indicate that IA is potentially involved in eribulin-induced vascular remodeling and thereby suggest previously unacknowledged role of IA in regulating the tumor vasculature after eribulin administration.

Major vascular resection in retroperitoneal sarcoma surgery.

Major blood vessels may be invaded either by primary sarcomas arising from the vessel wall or by secondary infiltration of a retroperitoneal sarcoma. The involvement of major blood vessels is not considered to be an absolute contraindication for surgical resection. The main issue when evaluating a possible major vascular resection is to balance the possible surgical morbidity with the expected survival benefit. This is strictly related to the tumor's biology and clinical behavior and to the patient's performance status and comorbidities. A multidisciplinary approach in a specialized center is mandatory when approaching a possible oncovascular resection for retroperitoneal sarcoma, given the rarity and the heterogeneity of these tumors.

Personalising sarcoma care using quantitative multimodality imaging for response assessment.

Over the last decades, technological developments in the field of radiology have resulted in a widespread use of imaging for personalising medicine in oncology, including patients with a sarcoma. New scanner hardware, imaging protocols, image reconstruction algorithms, radiotracers, and contrast media, enabled the assessment of the physical and biological properties of tumours associated with response to treatment. In this context, medical imaging has the potential to select sarcoma patients who do not benefit from (neo-)adjuvant treatment and facilitate treatment adaptation. Due to the biological heterogeneity in sarcomas, the challenge at hand is to acquire a practicable set of imaging features for specific sarcoma subtypes, allowing response assessment. This review provides a comprehensive overview of available clinical data on imaging-based response monitoring in sarcoma patients and future research directions. Eventually, it is expected that imaging-based response monitoring will help to achieve successful modification of (neo)adjuvant treatments and improve clinical care for these patients.

Laser speckle contrast analysis (LASCA) technology for the semiquantitative measurement of angiogenesis in in-ovo-tumor-model.

BACKGROUND: The process of angiogenesis is a key element for tumor growth and proliferation and therefore one of the determining factors for aggressiveness and malignancy. A better understanding of the underlying processes of tumor induced angiogenesis is crucial for superior cancer treatment. Furthermore, the PeriCam perfusion speckle imager (PSI) system high resolution (HR) model by PERIMED presents a noninvasive method for semi-quantitative measurement of blood perfusion, based on laser speckle contrast analysis (LASCA). Aim of the present study was to utilize the chick chorioallantoic membrane (CAM) model as an in-ovo-tumor-model which enables rapid neovascularization of tumors while allowing real-time observation of the microcirculation via LASCA. METHODS: Fertilized chicken eggs were grafted with embryonal/alveolar rhabdomyosarcoma cells or primary sarcoma tumors. The blood perfusion was measured before and after tumor growth using LASCA. The procedure is accelerated and simplified through the integrated PIMSoft software which provides real-time graphs and color-coded images during the measurement. RESULTS: Sarcoma cells and primary sarcoma tumors exhibited satisfactory growth processes on the CAM. LASCA visualized microcirculation accurately and enabled an extensive investigation of the angiogenic potential of sarcoma cells on the CAM. We were able to show that sarcoma cells and primary sarcoma tumors induced larger quantities of neovasculature on the CAM than the controls. CONCLUSIONS: The utilization of LASCA for the investigation of tumor angiogenesis within the CAM model appears to be a highly beneficial, cost-efficient and easily practicable procedure. The proposed model can be used as a drug-screening model for individualized cancer therapy, especially with regards to anti-angiogenic agents.

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.

Apatinib as targeted therapy for advanced bone and soft tissue sarcoma: a dilemma of reversing multidrug resistance while suffering drug resistance itself.

Bone and soft tissue sarcomas are rare malignant tumors originated from mesenchymal tissues. They harbor more than 50 distinct subtypes and differ in pathological features and clinical courses. Despite the significant improvements in modern multi-modality treatment, the outcomes and overall survival rates remain poor for patients with advanced, refractory, metastatic, or relapsed diseases. The growth and metastasis of bone and soft tissue sarcoma largely depend on angiogenesis, and VEGF/VEGFR pathway is considered as the most prominent player in angiogenesis. Therefore, blockade of VEGF/VEGFR pathways is a promising therapeutic strategy to retard neovascularization. Several VEGFR inhibitors have been developed and revealed their favorable anti-neoplastic effects in various cancers, but such desirable anti-tumor effects are not obtained in advanced sarcomas because of multiple reasons, such as drug tolerance, short duration of response, and severe adverse effects. Fortunately, preclinical and clinical studies have indicated that apatinib is a novel promising VEGFR2 inhibitor showing potent anti-angiogenic and anti-neoplastic activities in advanced sarcomas. Especially, apatinib has showed notable characteristics in multidrug resistance reversal, tumor regression, vascular normalization, immunosuppression alleviation, and enhancement of chemotherapeutic and radiotherapeutic effects. However, apatinib also gets struck in dilemma of reversing multidrug resistance of chemotherapeutic agents while suffering drug resistance itself, and several difficulties should be tackled before full use of apatinib. In this review, we discuss the outstanding characteristics and main predicaments of apatinib as targeted therapy in advanced sarcomas. Bone and soft tissue sarcomas are rare but malignant tumors originated from mesenchymal tissues. They harbor more than 100 distinct subtypes and differ in features of pathologies and clinical courses. Despite the significant improvements in modern multi-modality treatment, the outcomes and overall survival rates remain poor for patients with advanced, refractory, metastatic, or relapsed lesions. The growth and metastasis of bone and soft tissue sarcoma largely depend on angiogenesis and VEGF/VEGFR pathways play a pivotal role in angiogenesis. Therefore, blockade of VEGF/VEGFR pathways is a promising therapeutic strategy. Several VEGFR inhibitors have been developed and verified in clinical trials but with unfavorable outcomes. Fortunately, preclinical studies and clinical trials have indicated that apatinib is a novel promising VEGFR2 inhibitor showing potent anti-angiogenic and anti-neoplastic activities in advanced sarcomas. Actually, apatinib has showed notable characteristics in multidrug resistance reversal, tumor regression, vascular normalization, immunosuppression alleviation, enhancement of chemotherapeutic and radiotherapeutic effects. However, apatinib also gets struck in dilemma of reversing multidrug resistance of chemotherapeutic agents while suffering drug resistance itself, and several difficulties should be tackled before full use of apatinib. In this review, we discuss the outstanding characteristics and main predicaments of apatinib as targeted therapy in advanced sarcomas.

Effect of chemotherapy on cancer stem cells and tumor-associated macrophages in a prospective study of preoperative chemotherapy in soft tissue sarcoma.

BACKGROUND: Cancer stem cells (CSC) may respond to chemotherapy differently from other tumor cells. METHODS: This study examined the expression of the putative cancer stem cell markers ALDH1, CD44, and CD133; the angiogenesis marker CD31; and the macrophage marker CD68 in soft tissue sarcomas (STS) before and after 4 cycles of chemotherapy with doxorubicin and ifosfamide in 31 patients with high-grade soft tissue sarcoma in a prospective clinical trial. RESULTS: None of the markers clearly identified CSCs in STS samples. Macrophages represented a prominent component in viable tumor areas in pre-treatment STS biopsies, ranging from < 5 to > 50%. Furthermore, macrophages expressed CD44 and ALDH1. Macrophage density correlated with baseline maximum standardized uptake value (SUVmax) on fluoro-deoxyglucose positron emission tomography (PET) imaging. Pre-chemotherapy CD68 staining correlated positively with the baseline SUVmax, and negatively with the percent of viable tumor cells in post-chemotherapy resection samples. In particular, cases with more CD68-positive cells at biopsy had fewer viable tumor cells at resection, suggesting a better response to chemotherapy. CONCLUSIONS: In conclusion, ALDH1, CD44, and CD133 are not likely to be useful markers of CSCs in STS. However, our observation of infiltrating macrophages in STS specimens indicates that these immune cells may contribute significantly to STS biology and response to chemotherapy, and could provide a potential target of therapy. Future studies should investigate macrophage contribution to STS pathophysiology by cytokine signaling.

Influence of temporal parameters of DCE-MRI on the quantification of heterogeneity in tumor vascularization.

BACKGROUND: Evaluating heterogeneity in tumor vascularization through texture analysis could improve predictions of patients' outcome and response evaluation. PURPOSE: To investigate the influence of temporal parameters on texture features extracted from dynamic contrast-enhanced (DCE)-MRI parametric maps. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Twenty-five adults with soft-tissue sarcoma (STS), median age: 68 years. FIELD STRENGTH/SEQUENCE: DCE-MRI acquisition using a CAIPIRINHA-Dixon-TWIST-VIBE sequence at 1.5T (temporal resolutions: 2 sec, duration: 5 min). ASSESSMENT: The area under time-intensity curve (AUC) and Ktrans maps were generated for several temporal resolution (dt = 2 sec, 4 sec, 6 sec, 8 sec, 10 sec, 12 sec, 20 sec) and scan durations (T = 3 min, 4 min, 5 min for a 6-sec sampling) by downsampling and truncating the initial DCE-MRI sequence. Tumor volume was manually segmented and propagated on all parametric maps. Thirty-two first- and second order-texture features were extracted per map to quantify the intratumoral heterogeneity. STATISTICAL TESTS: The influence of temporal parameters on texture features was studied with repeated-measures analysis of variance (or nonparametric equivalent). The dispersion of each texture feature depending on temporal parameters was estimated with coefficients of variation (CVs). The performances of multivariate models to predict the response to chemotherapy (ie, binary logistic regression based on the baseline texture features) were compared. RESULTS: The temporal resolution had a significant influence on 12/32 (37.5%) and 14/32 (43.8%) texture features evaluated on AUC and Ktrans maps, respectively (range of P < 0.0001-0.0395). Scan duration had a significant influence on 23/32 (71.9%) texture features from Ktrans map (range of P < 0.0001-0.0321). Dispersion was high (mean CV >0.5) with sampling for 2/32 (6.3%) and 10/32 (31.3%) features from AUC and Ktrans maps, respectively; and with truncating for 6/32 (18.8%) features from Ktrans map. The area under the receiver operating characteristics curve of predictive models ranged from 0.77 (95% confidence interval [CI] = [0.54-1.00], with dt = 6 sec T = 4 min) to 0.90 (95% CI = [0.74-1.00], with dt = 6 sec T = 5 min). DATA CONCLUSION: The values of texture features extracted from DCE-MRI parametric maps can be influenced by temporal parameters, which can lead to variations in performance of predictive models. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1773-1788.

Functional imaging of tumor vasculature using iodine and gadolinium-based nanoparticle contrast agents: a comparison of spectral micro-CT using energy integrating and photon counting detectors.

Advances in computed tomography (CT) hardware have propelled the development of novel CT contrast agents. In particular, the spectral capabilities of x-ray CT can facilitate simultaneous imaging of multiple contrast agents. This approach is particularly useful for functional imaging of solid tumors by simultaneous visualization of multiple targets or architectural features that govern cancer development and progression. Nanoparticles are a promising platform for contrast agent development. While several novel imaging moieties based on high atomic number elements are being explored, iodine (I) and gadolinium (Gd) are particularly attractive because of their existing approval for clinical use. In this work, we investigate the in vivo discrimination of I and Gd nanoparticle contrast agents using both dual energy micro-CT with energy integrating detectors (DE-EID) and photon counting detector (PCD)-based spectral micro-CT. Simulations and phantom experiments were performed using varying concentrations of I and Gd to determine the imaging performance with optimized acquisition parameters. Quantitative spectral micro-CT imaging using liposomal-iodine (Lip-I) and liposomal-Gd (Lip-Gd) nanoparticle contrast agents was performed in sarcoma bearing mice for anatomical and functional imaging of tumor vasculature. Iterative reconstruction provided high sensitivity to detect and discriminate relatively low I and Gd concentrations. According to the Rose criterion applied to the experimental results, the detectability limits for I and Gd were approximately 2.5 mg ml-1 for both DE-EID CT and PCD micro-CT, even if the radiation dose was approximately 3.8 times lower with PCD micro-CT. The material concentration maps confirmed expected biodistributions of contrast agents in the blood, liver, spleen and kidneys. The PCD provided lower background signal and better simultaneous visualization of tumor vasculature and intratumoral distribution patterns of nanoparticle contrast agent compared to DE-EID decompositions. Preclinical spectral CT systems such as this could be useful for functional characterization of solid tumors, simultaneous quantitative imaging of multiple targets and for identifying clinically-relevant applications that benefit from the use of spectral imaging. Additionally, it could aid in the development nanoparticles that show promise in the developing field of cancer theranostics (therapy and diagnostics) by measuring vascular tumor biomarkers such as fractional blood volume and the delivery of liposomal chemotherapeutics.

Vascular Endothelial FSH Receptor, a Target of Interest for Cancer Therapy.

Improved molecular understanding of tumor microenvironment has resulted in the identification of various cancer cell targets for diagnostic and therapeutic interventions, including the receptor for the FSH, a glycoprotein hormone responsible for growth, maturation, and function of human reproductive system. The expression and localization of the FSH receptor (FSHR)-protein were associated with the tumor epithelial cells and/or with the peripheral tumor blood vessels. The available evidence indicates that in ovarian cancer, prostate cancer, and breast cancer, the tumor epithelial FSHR promotes proliferation, migration, and invasion of cancer cells. The vascular endothelial FSHR, detected in 11 types of solid tumors and 11 types of sarcomas, is involved in receptor-mediated transendothelial transport of FSH, tumor angiogenesis, and vascular remodeling. In contrast to intratumor vessels, which are abnormal and disorganized, the FSHR-positive blood microvessels are arranged in a hierarchical pattern: arterioles-capillaries-venules. The FSHR-positive blood vessels make connections between the intratumor vessels and the general blood circulation of patients. In this mini-review, I summarize these studies and discuss the rationale for developing a strategy for cancer therapy based on FSHR expressed on the luminal endothelial cell surface of blood vessels located in the peritumoral area rather than endothelial markers expressed in the core of tumors. Because FSHR is a common marker of peritumoral vessels, therapeutic agents coupled to anti-FSHR humanized antibodies should in principle be applicable to a wide range of tumor types.

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.

[A Case of Adult Undifferentiated Sarcoma of the Liver with Intraatrial Metastasis].

A 24-year-old woman was admitted to the hospital for abdominal pain. Abdominal contrast-enhanced computed tomography( CT)revealed a cystic mass measuring 11×8 cm in the left lobe of the liver with extravasation. Vascular embolization was performed, but extravasation remained on CT images. She was then transferred to our hospital. We performed an emergency extended left hepatectomy. Histopathological examination revealed solid proliferation of spindle-shaped cells. Immunohistochemical staining showed that the tumor cells were positive for vimentin and negative for AE1/AE3. Thus, a diagnosis of undifferentiated sarcoma was confirmed. Multiple recurrent tumors were recognized on CT images of the lung and right atrium taken 1 year and 10 months post-surgery. Partial resection of the tumor was performed for the right atrial mass, the left lingular segment, the left inferior lobe, and the right middle lobe. Pathological diagnosis confirmed metastasis of undifferentiated sarcoma from the liver. Chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide(VAC) was not effective, and the patient died 31 months after the primary surgery. Undifferentiated sarcoma of the liver is a rare malignant mesenchymal tumor, whose occurrence is extremely rare in adults. Although surgical treatment is the first choice, outcomes remain poor. Multimodality treatment should be used to improve the outcome.

Drug-eluting bead transarterial chemoembolization in the treatment for unresectable soft tissue sarcoma refractory to systemic chemotherapy: a preliminary evaluation of efficacy and safety.

PURPOSE: To preliminarily evaluate the clinical efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy. METHODS: Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs). Tumor response to DEB-TACE was assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. RESULTS: All DEB-TACE procedures were successfully performed for ten patients with 15 tumor lesions. The median follow-up duration was 19 months and the median survival time was 21 months (range 11-30 months). The 1- and 2-year OS rate was 90 and 30%, respectively. According to the guidance of mRECIST, complete response, partial response, stable disease and progressive disease were noted in zero (0%), three (30%), four (40%) and three (30%) patients, respectively. The disease control rate and objective response rate was 70 and 30%, respectively. There were no serious AEs in patients after DEB-TACE. CONCLUSIONS: Our data showed that DEB-TACE was effective and safe for patients with soft tissue sarcoma. Therefore, DEB-TACE can be considered as an alternative treatment option for unresectable soft tissue sarcoma refractory to conventionally systemic chemotherapy.

[Complex pelvic and sarcoma surgery with vascular replacement]. / Komplexe Becken- und Sarkomchirurgie mit Gefäßersatz.

Due to optimization of surgical techniques in surgical oncology and vascular surgery, the most modern approaches of anesthesia and intensive care medicine and effective multimodal therapeutic strategies, locally advanced malignant tumors are resected more frequently with a potentially curative intent. In the case of extensive tumors with infiltration of vital vascular structures or of structures which are crucial for extremity preservation, the necessary surgical procedure for complete tumor removal poses a major challenge for the surgeon and incorporates a high risk of perioperative morbidity for the patient. The decision to attempt tumor resection should therefore always be based on a concept considering all aspects of the malignant disease. The treating team should be highly experienced in this complex field of surgery, not only with respect to the surgical approach but also regarding the management of postoperative complications. In this article relevant aspects of decision making, surgical technique and postoperative outcome for malignant tumors involving vascular structures of the retroperitoneum and pelvis are presented.

Temporal changes in tumor oxygenation and perfusion upon normo- and hyperbaric inspiratory hyperoxia.

BACKGROUND: Inspiratory hyperoxia under hyperbaric conditions has been shown to effectively reduce tumor hypoxia and to improve radiosensitivity. However, applying irradiation (RT) under hyperbaric conditions is technically difficult in the clinical setting since RT after decompression may be effective only if tumor pO2 remains elevated for a certain period of time. The aim of the present study was to analyze the time course of tumor oxygenation and perfusion during and after hyperbaric hyperoxia. MATERIALS AND METHODS: Tumor oxygenation, red blood cell (RBC) flux for perfusion monitoring, and vascular resistance were assessed continuously in experimental rat DS-sarcomas by polarographic catheter electrodes and laser Doppler flowmetry at 1 and 2 atm (bar) of environmental pressure during breathing of pure O2 or carbogen (95 % O2 + 5 % CO2). RESULTS: During room air breathing, the tumor pO2 followed very rapidly within a few minutes the change of the ambient pressure during compression or decompression. With O2 breathing under hyperbaric conditions, the tumor pO2 increased more than expected based on the rise of the environmental pressure, although the time course was comparably rapid. Breathing carbogen, the tumor pO2 followed with a slight delay of the pressure change, and within 10 min after decompression the baseline values were reached again. RBC flux increased during carbogen breathing but remained almost constant with pure O2, indicating a vasodilation (decrease in vascular resistance) with carbogen but a vasoconstriction (increase in vascular resistance) with O2 during hyperbaric conditions. CONCLUSION: Since the tumor pO2 directly followed the environmental pressure, teletherapy after hyperbaric conditions does not seem to be promising as the pO2 reaches baseline values again within 5-10 min after decompression.

[COMBINATION OF VESSEL EMBOLIZATION AND CRYOTHERAPY IN SURGICAL TREATMENT OF SOFT TISSUE SARCOMAS].

The article analyzed the results of surgical treatment of 153 patients with soft tissue sarcomas. The surgery was complemented by preoperative embolization of vessels, which supplied the tumor, cryotherapy on the tumor and postoperative wound in 72 patients of main group. The control group consisted of 81 patients and there weren't any perioperative actions. It was shown, that more than 80% of soft tissue sarcomas had the main and mixed type of tumor blood supply. Partial and full reduction of blood flow could be obtained by embolization of the tumor in more than 50% patients. Combination of surgical and preoperative embolization of vessels and cryotherapy decreased the rate of local recurrence and increased the quantity of organosafe interventions.

Targeted therapy in sarcomas other than GIST tumors.

Non-GIST soft tissue sarcomas are a heterogeneous grouping of mesenchymal tumors that comprise less than 1% of adult malignancies. Treatment continues to be based on cytotoxic chemotherapy regimens. However, characterization of the molecular pathway deregulations that drive these tumors has led to the emergence of more customized treatment options. In this review, we focus on the multitude of molecular inhibitors targeting angiogenesis and cell cycle pathways being tested in clinical trials.