Metastatic Tumor Lesions Research Articles

Abstract 39: LCN2, CD133 expressions in breast cancer spinal bone metastasis and CD151, TWIST1, EPHA2 in lung metastasis: Prognostic value and organ-specific relapse

Abstract Purpose: Breast cancer most often recurs and metastasizes to the distal organs that had their primary tumors surgically excised. Due to heterogeneous nature of the breast cancer, metastasis organotropism has poorly understood. In this study, we assessed the specific cancer-related gene expression changes occurring with metastatic breast cancer recurrence to distant organs comparing with non-metastatic breast cancer. Experimental design: We develop a clinically relevant metastatic syngeneic mouse model using two cell lines 4T1-luc2 that can only metastasize to lung and 4T1.2-luc2 metastasized to bone and lung. After the primary mammary tumor surgically excised from mice, we monitor mice using IVIS imaging for metastatic tumor lesion development in the distant organs followed by MRI scan to detect spinal bone metastases. Animals were sacrificed to collect spines, bones, and lung lesions for molecular analysis. We also validate the gene expression data using the RNA-seq cohort data from the Roswell Park Cancer Institute patient samples with advanced breast cancer bone metastases and matched non-metastatic breast cancer. Results: Our cell lines, RNA-seq data analysis suggested that there are at least 50 genes which are statistically highly expressed in 4T1.2-luc2 compared to 4T1-luc2 cells. Out of which only a few genes are well established for cancer metastasis biology, include ANGPTL77, SERPINE2, TSPAN11, ESM1, LCN2 which are expressed more than 8 fold in 4T1.2-luc2 compared to 4T1-luc2 cells. To our surprise, we found that most of these genes are differentially expressed when metastasized to distant organ. Our data revealed that LCN2 (7 fold) and CD133 (above 20 fold) are overexpressed in the spine and bone compared to the primary or lung met lesions formed by 4T1.2-luc2. Conversely, LCN2 and CD133 genes are downregulated in breast cancer lung metastasis tissues, whereas CD151, EPHA2, and TWIST1 genes are highly overexpressed in lung metastatic lesion compared to primary, bone or spine. Further, the RNA-seq data of patient samples explained that LCN2, CD133 expressions are significantly higher (8 out of 10 patients) in advanced breast cancer bone metastases compared with matching non-metastatic breast cancer. Conclusion: Our data suggested that LCN2, CD133 would be a prognostic marker for breast cancer spinal bone metastasis, whereas CD151, TWIST1, EPHA2 would be a prognostic marker for lung metastasis and organ-specific relapse. Citation Format: Aparna Maiti, Nitai C. Hait. LCN2, CD133 expressions in breast cancer spinal bone metastasis and CD151, TWIST1, EPHA2 in lung metastasis: Prognostic value and organ-specific relapse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 39.

Tunable cytotoxic aptamer–drug conjugates for the treatment of prostate cancer

Therapies that can eliminate both local and metastatic prostate tumor lesions while sparing normal organ tissue are desperately needed. With the goal of developing an improved drug-targeting strategy, we turned to a new class of targeted anticancer therapeutics: aptamers conjugated to highly toxic chemotherapeutics. Cell selection for aptamers with prostate cancer specificity yielded the E3 aptamer, which internalizes into prostate cancer cells without targeting normal prostate cells. Chemical conjugation of E3 to the drugs monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) yields a potent cytotoxic agent that efficiently kills prostate cancer cells in vitro but does not affect normal prostate epithelial cells. Importantly, the E3 aptamer targets tumors in vivo and treatment with the MMAF-E3 conjugate significantly inhibits prostate cancer growth in mice, demonstrating the in vivo utility of aptamer-drug conjugates. Additionally, we report the use of antidotes to block E3 aptamer-drug conjugate cytotoxicity, providing a safety switch in the unexpected event of normal cell killing in vivo.

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model.

Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer.

Association of predicted pathogenic mutations in mitochondrial ND genes with distant metastasis in NSCLC and colon cancer

Cancer cells have more mutations in their mitochondrial DNA (mtDNA) than do normal cells, and pathogenic mutations in the genes encoding mitochondrial NADH dehydrogenase (ND) subunits have been found to enhance the invasive and metastatic ability of various tumour cells in animal experiments. However, it is unknown whether single-nucleotide variants (SNVs) of the ND genes that decrease complex I activity are involved in distant metastasis in human clinical samples. Here, we demonstrated the enhancement of the distant metastasis of Lewis lung carcinoma cells by the ND6 13885insC mutation, which is accompanied by the overexpression of metastasis-related genes, metabolic reprogramming, the enhancement of tumour angiogenesis and the acquisition of resistance to stress-induced cell death. We then sequenced ND genes in primary tumour lesions with or without distant metastases as well as metastatic tumour lesions from 115 patients with non-small cell lung cancer (NSCLC) and colon cancer, and we subsequently selected 14 SNVs with the potential to decrease complex I activity. Intriguingly, a significant correlation was observed (P < 0.05 by Chi-square test) between the incidence of the selected mutations and distant metastasis. Thus, these results strongly suggest that pathogenic ND gene mutations participate in enhancing distant metastasis in human cancers.

Pathological processes and therapeutic advances in radioiodide refractory thyroid cancer.

While in most patients with non-medullary thyroid cancer (TC), disease remission is achieved by thyroidectomy and ablation of tumor remnants by radioactive iodide (RAI), a substantial subgroup of patients with metastatic disease present tumor lesions that have acquired RAI resistance as a result of dedifferentiation. Although oncogenic mutations in BRAF, TERT promoter and TP53 are associated with an increased propensity for induction of dedifferentiation, the role of genetic and epigenetic aberrations and their effects on important intracellular signaling pathways is not yet fully elucidated. Also immune, metabolic, stemness and microRNA pathways have emerged as important determinants of TC dedifferentiation and RAI resistance. These signaling pathways have major clinical implications since their targeting could inhibit TC progression and could enable redifferentiation to restore RAI sensitivity. In this review, we discuss the current insights into the pathological processes conferring dedifferentiation and RAI resistance in TC and elaborate on novel advances in diagnostics and therapy to improve the clinical outcome of RAI-refractory TC patients.

Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas

The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs). Using brain-seeking patient-derived melanoma cells and real-time in vivo imaging, we show a widespread distribution of micrometastases and macrometastases in the brain, recapitulating the progression of multifoci metastases seen in patients. We armed MSCs with different oHSV variants (MSC-oHSV) and found that intracarotid administration of MSC-oHSV, but not of purified oHSV alone, effectively tracks metastatic tumor lesions and significantly prolongs the survival of brain tumor-bearing mice. In a syngeneic model of melanoma brain metastasis, a combination of MSC-oHSV and PD-L1 blockade increases IFNγ-producing CD8+ tumor-infiltrating T lymphocytes and results in a profound extension of the median survival of treated animals. This study thus demonstrates the utility of MSCs as OV carriers to disseminated brain lesions, and provides a clinically applicable therapeutic platform to target melanoma brain metastasis.

Abstract 2187: A pro-nanodrug with intratumoral reconstitution and intracellular delivery beyond therapy-resistance molecular pumps

Abstract Tumor metastases to distant organs pose a serious challenge to cancer treatment. The metastatic tumor lesions are less accessible to cancer drugs and the malignant cells often quickly develop therapy resistance. To address both biological and drug transport concerns in cancer treatment, we have developed a novel composite pro-nanodrug to provide sustained intra-tumoral assembly of nanotherapeutics, and tested its anti-cancer efficacy in murine models of breast cancer metastases to the lung and liver. Specifically, large payloads of polymeric doxorubicin (pDox) pro-drug were packaged as single molecules into a porous silicon microparticles that can be enriched in tumor tissue in the forms of vascular and cellular depots. Once inside the tumor, the pDox molecules self-assemble into nanoparticles that are released into the tissue where they are effectively internalized by tumor cells. The nanoparticulate prodrug is transported through the vesicular system, and doxorubicin is cleaved from the polymer and released in the immediate proximity of the nucleus beyond the reach of the drug efflux pumps. In vivo efficacy studies demonstrated that the pro-nanodrug was effective in treating metastatic tumors with or without expression of the multi-drug resistant genes. Citation Format: Rong Xu, Mauro Ferrari, Haifa Shen. A pro-nanodrug with intratumoral reconstitution and intracellular delivery beyond therapy-resistance molecular pumps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2187. doi:10.1158/1538-7445.AM2017-2187

Effects of myeloid specific deficiency of FBXW7 on lung metastasis of murine melanoma

Objective: To investigate the effects of myeloid-specific deficiency of FBXW7 on lung metastasis of murine B16F10 melanoma and its mechanisms. Methods: Mice carrying the floxed allele of FBXW7 and lysozyme M-Cre were used for generation of mice with myeloid cell-specific deletion of FBXW7. Mouse genotypes were examined by genomic DNA PCR. B16F10 cells in PBS were injected into the tail vein of Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. After 14 d, the mice were sacrificed, and the lungs were removed and weighed. B16F10 tumor colonies in the lungs were counted. The myeloid cells were analyzed by flow cytometry. Results: Myeloid-specific deficiency of FBXW7 mice were generated successfully, as FBXW7 expressions in peritoneal macrophages and bone marrow-derived macrophages (BMDMs) of Lysm+FBXW7f/f mice were knockdown. Flow cytometry results showed the deletion of FBXW7 in myeloid lineages did not affect the development of myeloid immune cell subsets. Metastasis was reduced in Lysm+FBXW7 f/f mice compared with control mice. The number of tumor colonies was 165±42, 122±12 respectively. The proportion of metastasis-associated macrophages (MAM) in the lungs of Lysm+FBXW7 f/f mice was reduced [(23.15±7.59)% vs (13.13±2.26)%], while the proportion of resident macrophages was increased [(5.426±0.42)% vs (10.42±1.90)%]. The proportion of myeloid-derived suppressor cells in the lung showed no difference between Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. Conclusion: Myeloid-specific deficiency of FBXW7 can inhibit lung metastasis of B16F10 melanoma in mice, and the mechanism may be associated with regulation of MAM in the metastatic tumor lesions.

Multivariate Feature Selection of Image Descriptors Data for Breast Cancer with Computer-Assisted Diagnosis.

Breast cancer is an important global health problem, and the most common type of cancer among women. Late diagnosis significantly decreases the survival rate of the patient; however, using mammography for early detection has been demonstrated to be a very important tool increasing the survival rate. The purpose of this paper is to obtain a multivariate model to classify benign and malignant tumor lesions using a computer-assisted diagnosis with a genetic algorithm in training and test datasets from mammography image features. A multivariate search was conducted to obtain predictive models with different approaches, in order to compare and validate results. The multivariate models were constructed using: Random Forest, Nearest centroid, and K-Nearest Neighbor (K-NN) strategies as cost function in a genetic algorithm applied to the features in the BCDR public databases. Results suggest that the two texture descriptor features obtained in the multivariate model have a similar or better prediction capability to classify the data outcome compared with the multivariate model composed of all the features, according to their fitness value. This model can help to reduce the workload of radiologists and present a second opinion in the classification of tumor lesions.

Possibilities of contrast- enhanced ultrasound (CEUS) for evaluation of the success of percutaneous treatments of malignant liver lesions using special perfusion software

Aim: Using new perfusion software for evaluation of the success of percutaneous treatments of malignant liver tumor lesions with CEUS.

A computational tool for evaluating HIFU safety.

High Intensity Focused Ultrasound (HIFU) is a noninvasive treatment for therapeutic applications, in particular the treatment of either benign or malignant tumor lesions. HIFU treatment is based on the power of a focused ultrasound beam to locally heat biological tissues over a necrotic level with minimal impact on the surrounding tissues. Therapies based on HIFU are becoming widely spread in the panorama of options offered by the Health Care System. Consequently, there is an ever increasing need to standardise quality assurance protocols and to develop computational tools to evaluate the output of clinical HIFU devices and ensuring safe delivery of HIFU treatment. Goal of this study is the development of a computational tool for HIFU ablation therapy to assure safety of the patient and effectiveness of the treatment. The simulated results provide information about the behaviour of the focalized ultrasound in their interaction with different biological tissues. Numerical simulation represents a useful approach to predict the heath deposition and, consequently, to assess the safety and effectiveness of HIFU devices.

Magnetic resonance guided focused ultrasound surgery for pain palliation of bone metastases: early experience of clinical application in China

To evaluate the safety and efficacy of magnetic resonance guided focused ultrasound surgery (MRgFUS) in treatment for pain palliation of bone metastases. Eighty-one patients of painful bone metastases were volunteered to screen for this study in Shanghai General Hospital from June 2014 to February 2015. Twenty-three patients among them were treated by MRgFUS, who was more than 18-years old, having the ability to fully understand the informed consent of the research, suffering with pain of numeric rating scale (NRS) ≥ 4, non-received radiotherapy or chemotherapy for pain palliation of bone metastases in the past two weeks. The NRS, the standard question of Brief Pain Inventory (BPI-QoL), and the standard question of Europe Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Bone Metastases 22 (EORTC QLQ-BM22) were respectively recorded before and 1-week, 1-month, 3-month after the treatment. The related adverse events of MRgFUS were observed and recorded in 3 months after the treatment as well. (1)Twenty-three metastatic bone tumor lesions of 23 patients were treated by MRgFUS, the treatment data was as follows: the mean treatment time was (88 ± 33) minutes, the mean sonication number was 13 ± 8. (2) Adverse events included: pain in therapy area 3/23, which spontaneous relieving within one week; numbness in lower limb (1/23), which relieved after physiotherapy. (3) The NRS of before treatment and at 1-week, 1-month, and 3-month after treatment respectively was 6.0 ± 1.5, 3.7 ± 1.7,3.1 ± 2.0, and 2.2 ± 1.0,which significantly decreased after the treatment (P<0.01). (4) The BPI-QoL score of before treatment and at 1-week, 1-month, and 3-month after treatment respectively was 39 ± 16, 27 ± 18, 26 ± 18, and 21 ± 18, which significantly decreased after the treatment (P<0.01). (5) The EORTC QLQ-BM22 score of before treatment and at 1-week, 1-month, and 3-month after treatment respectively was 52 ± 13, 44 ± 12, 42 ± 12, and 39 ± 12, which also significantly decreased after the treatment (P<0.01). MRgFUS can be used as a non-invasive, safe, and effective method for treating painful bone metastases. Its clinical benefits of pain palliation and patient's quality of life improving are sustained after the treatment at least to 3 months.

Comparison of Two Types of Liquid Biopsies in Patients With Hepatocellular Carcinoma Awaiting Orthotopic Liver Transplantation

IntroductionOrthotopic liver transplantation (OLT) is considered one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). It has been shown that more than 10% of transplanted individuals suffer relapse during the first year after surgery and most of them die because of the tumor. The circulating tumor cells (CTCs) are the main source of recurrences as they disseminate from a primary or metastatic tumor lesion through peripheral blood. We aimed to determine the concentration of CTCs in peripheral blood in these patients by 2 different approaches: the CellSearch and the IsoFlux systems to assess their applicability to this disease monitoring. Patients and MethodsA comparative study was conducted in 21 patients with HCC eligible for liver transplantation according to the Milan criteria, whose peripheral blood was processed by the CellSearch and the IsoFlux systems. ResultsCTCs were isolated in 1 of the 21 patients (4.7%) by the CellSearch system and in 19 of the 21 patients (90.5%) by the IsoFlux method. The comparison of both methods using Bland-Altman plot shows that there is not consistency in the determination of CTCs in our patients, finding a proportional bias between them. ConclusionThe results obtained by both CTCs isolation systems are not interchangeable nor transferable. The CellSearch system does not seem to be the ideal approach for studying CTCs in patients with HCC. The IsoFlux system displays greater sensitivity in the identification of CTCs and might become an important tool in patient management.

Potential Clinical Implications of Circulating Tumor Cells

The circulating tumor cells (CTCs) are derived from primary or metastatic tumor lesions and can be detected in the peripheral blood. With certain specific features, CTCs can,to certain extent, reflect the progression and invasiveness of tumors. Detection of CTCs may provide a powerful and noninvasive approach for diagnosing neoplastic disease, identifying drug sensitivity, and enabling real-time treatment monitoring and prognosis prediction. Improvements in cell isolation and molecular identification will enable a broad range of clinical applications.

Highlights of This Issue

Simultaneous blockade of MAPK and PI3K pathway signaling in tumors can preempt adaptive resistance and achieve synergistic cell killing. Clinical application of this approach, however, has proven elusive due to an increased prevalence of dose-limiting toxicity. Dreaden and colleagues address this unmet need by developing a tumor-targeting nanoscale drug formulation based layer-by-layer (LbL) self-assembly that horizontally blocks MAPK and PI3K signaling in mouse models of breast carcinoma. The authors observed further enhanced drug synergy following co-encapsulation, tumor-targeted drug delivery, and disease stabilization following systemic administration—importantly—in the absence of hepatic and renal toxicity observed with the free drug combination.Peripheral neuropathy is a common adverse effect of chemotherapy that can lead to possible cessation of therapy with no effective treatments or genetic markers to predict those at risk. Using an integrative genome-wide approach that included cell-based and patient data led to the identification of genes contributing to paclitaxel induced peripheral neuropathy in Asians and common to Europeans and Asians. Two genes, AIPL1 and BCR, were functionally validated in a stem cell-derived neuronal cell model. This approach may help prioritize target genes associated with peripheral neuropathy, leading to the development of future neuroprotective agents and personalized cancer treatments.The human papillomavirus (HPV) oncoproteins are attractive targets for cancer immunotherapy, but evidence that human T cells directed against these antigens can target HPV+ tumors is limited. Draper and colleagues identified from the TIL of a patient with metastatic anal cancer a high avidity T-cell receptor (TCR) targeting HPV-16 E6. They found that T cells genetically engineered to express this TCR were capable of recognizing HPV-16+ oropharyngeal and cervical cancer cell lines. This research provides the preclinical basis for a clinical trial of TCR genetically engineered T cells targeting HPV-16 E6 that is now active.Tumor development is a dynamic process with genetic heterogeneity observed both in space and time. To investigate the genomic landscape of pheochromocytoma, Crona and colleagues investigated 136 tumor samples from 94 patients and describe genetic heterogeneity at all levels: between patients, between different tumor lesions of the individual patient, and within tumor lesions. Of particular notice are the observed pregnant differences between paired primary and metastatic tumor lesions. Clonal classification allowed for reconstructing the life history of individual tumors identifying somatic mutations as well as specific copy number losses as early events in pheochromocytoma tumorigenesis.

Whole-brain radiation fails to boost intracerebral gefitinib concentration in patients with brain metastatic non-small cell lung cancer: a self-controlled, pilot study.

Whole-brain radiation therapy (WBRT) is generally considered as an efficient strategy to improve blood-brain barrier (BBB) permeability by damaging BBB structure and is therefore, used as a promising pretreatment of chemotherapy. However, the impact of radiotherapy on leaky BBB is still controversial for the reason that BBB of metastatic brain tumor lesion had been breached by tumor metastasizing. Herein, we conducted a self-controlled study to evaluate the effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). A prospective self-controlled research was performed. Radiation-naive NSCLC patients with BM were enrolled and treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for 2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were collected on day 15 and 29 after the initiation of gefitinib treatment. The concentrations of gefitinib in these samples were measured by HPLC. Three patients were enrolled and evaluated. The concentrations of gefitinib in plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no significant change was noted in the CSF-to-plasma ratios of gefitinib before and after WBRT (2.79 ± 1.47 vs. 2.35 ± 1.74 %, p = 0.123). The WBRT may not affect the BBB permeability by determining the concentration of gefitinib in NSCLC patients with BM.

Evaluation of targeted therapies in advanced breast cancer: the need for large-scale molecular screening and transformative clinical trial designs.

Breast cancer (BC) has been classified into four intrinsic subtypes through seminal studies employing gene expression profiling analysis of primary tumours, namely the luminal A and B subtypes, the human epidermal growth factor receptor 2-like subtype and the basal-like subtype. More recently, the emergence of high-throughput genomic sequencing techniques, such as next-generation or massive parallel sequencing has expanded our understanding of the complex genomic landscapes of BC, with marked intertumour heterogeneity seen among different patients. In addition, increasing evidence indicates intratumour heterogeneity, with molecular differences observed within one patient, both spatially and longitudinally. These phenomena have an impact on the clinical development of molecularly targeted agents, with the classical paradigm of population-based clinical trials being no longer efficient. In the era of genomically driven oncology, three complementary tools can accelerate the clinical development of targeted agents for advanced BC as follows: (i) the implementation of molecular profiling of metastatic tumour lesions, as exemplified by the AURORA (Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer) programme; (ii) serial assessments of circulating tumour DNA, allowing a more thorough molecular interrogation of metastatic tumour burden; and (iii) new innovative clinical trial designs able to address the challenges of the increasing molecular fragmentation of BC.

Assessment of treatment response using Computed Tomography (CT) tumor volume measurements and lesion number in metastatic urothelial carcinoma (mUC) patients (pts) receiving cabozantinib.

e15503 Background: Assessment of tumor burden change is crucial in clinical trials and patient care. We compared cabozantinib-induced volume changes of all metastatic tumor lesions, total tumor les...

Bullous pemphigoid in Dermatology Departments of Silesia in years 2001-2014

Summary Introduction. Bullous pemphigoid (BP) is the most common disease from a group of bullous dermatoses. It affects mostly elderly people and the relative risk of disease devel- opment in people at the age 90 is 300-fold higher than in individuals who are 60 years old. It is supposed, that 15-20% of patients with BP may have malignant internal tumor and skin lesions can even precede the recognition of malignancy. Aim. The aim of this retrospective study was to assess the occurrence of BP in relation to age of patients and concomitant systemic diseases, including neoplastic disorders. Further analysis gives a review of therapeutic options and the efficacy of these modalities. Material and methods. A study group comprised of 120 patients who were diagnosed with BP: 74 female and 46 male patients. The mean age of patient was 71.13 ± 11.8. Results. Co-existing of other disease was reported in 87.11% of patients and the his- tory towards neoplastic disorder (active or previously treated) was positive in 19.8% of patients. In therapy of the disease, the drug of choice was Methylprednisolone. Other ther- apeutic options were also glucocorticoids (Dexamethasone, Prednisone, Triamcinolone), immunosuppressive agents (Cyclophosphamide, Chlorambucil or Azathioprine), antibiot- ics (Erythromycin, Doxycycline, Ceftriaxone), niacin and Dapsone. Conclusions. Clinical presentation of BP is distinguished and the recognition of the disease should be always supplemented by diverse diagnostic tests towards potent and hidden tumor. Although, glucocorticoids have remained a first choice therapy with good effects, further studies are necessary to establish the efficacy of other therapeutic mo- dalities.

Evaluation of Therapeutic Effect of Contrast-enhanced Ultrasonography in Hepatic Carcinoma Radiofrequency Ablation and Comparison with Conventional Ultrasonography and Enhanced Computed Tomography

Objective This paper aims to discuss the evaluation of the therapeutic effect of contrast-enhanced ultrasonography (CEUS) in radiofrequency ablation (RFA) for liver cancer and its application value. Methods A total of 80 patients (120 hepatic malignant tumor lesions) were treated using RFA, and CEUS was conducted on the liver before and after the treatment. Sixty-five patients (85/120 tumor lesions) had primary hepatic carcinoma and 11 (30/120 tumor lesions) had metastatic hepatic carcinoma (6 cases of 15 lesions had colorectal carcinoma, 3 cases of 8 lesions had lung carcinoma, and 2 cases of 7 lesions had gastric carcinoma). Four patients (5 lesions) had recurrence. Prior to the treatment, CEUS accurately guided the RFA of lesions, and after the treatment, the accuracy of CEUS was compared with conventional ultrasonography and enhanced computed tomography (CT). Results After the RFA, there were two cases of bile leakage, two cases of bleeding, and three cases of hydrothorax, and 20 cases had fever. In the CEUS performed after the operation, 114 of the 120 lesions (94.6%) were not filled with contrast agent in the arterial phase, venous phase, and delayed phase, indicating that the tumor lesions were totally inactivated. In the remaining six lesions, the arterial phase was enhanced partially on the edge, indicating suspected partial residues of tumor lesions. The final diagnosis was based on the aforementioned two kinds of imaging examinations in combination with the level of tumor markers, needle biopsy, and follow-up visits of over 1 month. Based on the therapeutic effects on the tumor after the operation with the final diagnosis as the standards, the accuracy of CEUS was 94.6%, whereas that of contrast-enhanced CT (CECT) and conventional ultrasonography was 93.4% and 60.5%, respectively. A comparative analysis was performed, which indicated that the difference between CEUS and conventional ultrasonography was of statistical significance (χ 2 = 5.42, p 2 = 5.14, p 2 = 7.54, p > 0.05). Conclusion CEUS has important value of clinical application both prior to and after RFA operations. Prior to the operation, CEUS can accurately guide the RFA treatment, whereas after the operation, CEUS is an important method to evaluate the inactivation after the treatment, and can be an important means for follow-up visits for partial treatment of hepatic carcinoma.