Recurrent Ureterosciatic Herniation Causing Right Obstructive Uropathy.

Sciatic hernias are unusual, challenging to diagnose, and can present some treatment dilemmas. Sciatic hernias containing the ureter are even less common. Symptoms are variable from renal fossa pain, mild or severe pelvic pain, neuropathic pain, or dysesthesias. Although stenting alone can be a treatment option for this condition, in cases where symptoms or ureteral obstruction relapse after initial treatment, sciatic hernioplasty must be considered as the definitive treatment. This article presents the case of a female patient who presented with a history of nonspecific abdominal pain and was diagnosed with a right-sided ureterosciatic hernia. This was managed with a ureteral stent for reduction of herniated ureteral content, but after recurrence, laparoscopic sciatic hernioplasty was performed. The patient was pain-free and without obstructive uropathy at the one-year follow-up.

Primary Chemoradiotherapy Treatment (PCRT) for HER2+ and Triple Negative Breast Cancer Patients: A Feasible Combination.

Primary systemic treatment (PST) downsizes the tumor and improves pathological response. The aim of this study is to analyze the feasibility and tolerance of primary concurrent radio−chemotherapy (PCRT) in breast cancer patients. Patients with localized TN/HER2+ tumors were enrolled in this prospective study. Radiation was delivered concomitantly during the first 3 weeks of chemotherapy, and it was based on a 15 fractions scheme, 40.5 Gy/2.7 Gy per fraction to whole breast and nodal levels I-IV. Chemotherapy (CT) was based on Pertuzumab−Trastuzumab−Paclitaxel followed by anthracyclines in HER2+ and CBDCA-Paclitaxel followed by anthracyclines in TN breast cancers patients. A total of 58 patients were enrolled; 25 patients (43%) were TN and 33 patients HER2+ (57%). With a median follow-up of 24.2 months, 56 patients completed PCRT and surgery. A total of 35 patients (87.5%) achieved >90% loss of invasive carcinoma cells in the surgical specimen. The 70.8% and the 53.1% of patients with TN and HER-2+ subtype, respectively, achieved complete pathological response (pCR). This is the first study of concurrent neoadjuvant treatment in breast cancer in which three strategies were applied simultaneously: fractionation of RT (radiotherapy) in 15 sessions, adjustment of CT to tumor phenotype and local planning by PET. The pCR rates are encouraging.

Surface-Enhanced Raman Scattering (SERS) Spectroscopy for Sensing and Characterization of Exosomes in Cancer Diagnosis.

Exosomes are emerging as one of the most intriguing cancer biomarkers in modern oncology for early cancer diagnosis, prognosis and treatment monitoring. Concurrently, several nanoplasmonic methods have been applied and developed to tackle the challenging task of enabling the rapid, sensitive, affordable analysis of exosomes. In this review, we specifically focus our attention on the application of plasmonic devices exploiting surface-enhanced Raman spectroscopy (SERS) as the optosensing technique for the structural interrogation and characterization of the heterogeneous nature of exosomes. We summarized the current state-of-art of this field while illustrating the main strategic approaches and discuss their advantages and limitations.

Correction: Metabolic pathway for the universal fluorescent recognition of tumor cells.

[This corrects the article DOI: 10.18632/oncotarget.18551.].

Adaptive metabolic pattern biomarker for disease monitoring and staging of lung cancer with liquid biopsy.

In this manuscript, we demonstrate the applicability of a metabolic liquid biopsy for the monitoring and staging of patients with lung cancer. This method provides an unbiased detection strategy to establish a more precise correlation between CTC quantification and the actual burden of disease, therefore improving the accuracy of staging based on current imaging techniques. Also, by applying statistical analysis techniques and probabilistic models to the metabolic status and distribution of peripheral blood mononuclear cell (PBMC) populations "perturbed" by the presence of CTCs, a new category of adaptive metabolic pattern biomarker (AMPB) is described and unambiguously correlated to the different clinical stages of the patients. In fact, this strategy allows for classification of different categories of disease within a single stage (stage IV) before computed tomography (CT) and positron emission tomography (PET) scans and with lower uncertainty.

Direct surface-enhanced Raman scattering (SERS) spectroscopy of nucleic acids: from fundamental studies to real-life applications.

Plasmonic optical biosensors for the analysis of nucleic acids have drawn a great deal of interest in nanomedicine because of their capability to overcome major limitations of conventional methods. Within this realm, surface-enhanced Raman scattering (SERS)-based sensing is progressively emerging as a powerful analytical tool beyond the basic grounds of academia to viable commercial products. SERS benefits from the synergistic combination between the intrinsic structural specificity and experimental flexibility of Raman spectroscopy, the extremely high sensitivity provided by plasmonic nanomaterials, and the tremendous advances in nanofabrication techniques and spectroscopic instrumentation. SERS application to nucleic acids analysis has been largely restricted to indirect sensing approaches, where a SERS reporter and oligonucleotide ligands are typically combined onto the nanomaterials to enable extrinsic detection of the target sequences. On the other hand, the acquisition of the intrinsic SERS vibrational fingerprint of nucleic acids (direct sensing) has traditionally suffered from major limitations. However, recent years have witnessed a burst of interest in this area, largely driven by the efforts to address key reproducibility and sensitivity issues. In this tutorial review, we summarize and discuss the most recent cutting-edge research in the field of direct SERS sensing of nucleic acids by coherently organising the diverse data reported in the literature in a structurally logical fashion.

Metabolic pathway for the universal fluorescent recognition of tumor cells.

Quantification of circulating tumor cells (CTCs) in blood samples from cancer patients is a non-invasive approach to monitoring the status of the disease. Most of the methods proposed in the recent years are phenomenological and rely on the use of antibodies labelled with fluorophores, magnetic particles, or immobilized on surfaces to capture the CTCs. Herein, we designed and optimized a method that employs a glucose analogue labelled with a fluorophore which takes advantage of the different metabolic pathways of cancer cells to discern them from normal ones. Notably, we demonstrate that fluorescence signal in tumor cells can be greatly maximized by applying hyperoxia conditions without damaging the cells. These results are demonstrated by means of confocal fluorescence and flow-cytometry measurements in peripheral blood mononuclear cells (PBMC) extracted after Ficoll of human blood samples and spiked with a known concentration of MCF-7 tumor cells.

SERS Quantification and Characterization of Proteins and Other Biomolecules.

Changes in protein expression levels and protein structure may indicate genomic mutations and may be related to some diseases. Therefore, the precise quantification and characterization of proteins can be used for disease diagnosis. Compared with several other alternative methods, surface-enhanced Raman scattering (SERS) spectroscopy is regarded as an excellent choice for the quantification and structural characterization of proteins. Herein, we review the main advance of using plasmonic nanostructures as SERS sensing platform for this purpose. Three design approaches, including direct SERS, indirect SERS, and SERS-encoded nanoparticles, are discussed in the direction of developing new precise approaches of quantification and characterization of proteins. While this Review is focused on proteins, in order to highlight concepts of SERS-based sensors also detection of other biomolecules will be discussed.

Smelling, Seeing, Tasting-Old Senses for New Sensing.

The senses are the physiological mechanisms of perception that enable an organism to interact with the surrounding media. For centuries, humans have utilized these senses in science; vision and olfaction have been used the most extensively in laboratories followed by gustation and somatosensation, whereas audition has only rarely been employed. Most of these applications of senses were developed spontaneously based on the natural behavior of the chemistry of the reactants producing changes in scent, taste, or color. In recent years, by exploiting the outstanding properties of nanoparticles, many groups have demonstrated alternative sensing scenarios where the detection limits are remarkably improved, enabling the recognition of hazardous substances by mere sight, smell, or taste. Such alternative sensing approaches can be divided into two main groups: (i) methods that identify a single analyte by engineering a reaction that promotes a change in color or the generation of a characteristic scent, and (ii) methods that emulate or even improve mammalian senses, especially those related to taste and smell. In this Perspective, we discuss the context of each technology, present prominent examples, and evaluate the complexities, potential pitfalls, and opportunities presented by different re-engineering strategies.

Optofluidic device for the quantification of circulating tumor cells in breast cancer.

Metastatic cancer patients require a continuous monitoring during the sequential treatment cycles to carefully evaluate their disease evolution. Repetition of biopsies is very invasive and not always feasible. Herein, we design and demonstrate a 3D-flow focusing microfluidic device, where all optics are integrated into the chip, for the fluorescence quantification of CTCs in real samples. To test the chip performance, two cell membrane targets, the epithelial cell adhesion molecule, EpCAM, and the receptor tyrosine-protein kinase, HER2, are selected. The efficiency of the platform is demonstrated on cell lines and in a variety of healthy donors and metastatic-breast cancer patients.

Conformational SERS Classification of K-Ras Point Mutations for Cancer Diagnostics.

Point mutations in Ras oncogenes are routinely screened for diagnostics and treatment of tumors (especially in colorectal cancer). Here, we develop an optical approach based on direct SERS coupled with chemometrics for the study of the specific conformations that single-point mutations impose on a relatively large fragment of the K-Ras gene (141 nucleobases). Results obtained offer the unambiguous classification of different mutations providing a potentially useful insight for diagnostics and treatment of cancer in a sensitive, fast, direct and inexpensive manner.

Surface-Enhanced Raman Scattering Surface Selection Rules for the Proteomic Liquid Biopsy in Real Samples: Efficient Detection of the Oncoprotein c-MYC.

Blood-based biomarkers (liquid biopsy) offer extremely valuable tools for the noninvasive diagnosis and monitoring of tumors. The protein c-MYC, a transcription factor that has been shown to be deregulated in up to 70% of human cancers, can be used as a robust proteomic signature for cancer. Herein, we developed a rapid, highly specific, and sensitive surface-enhanced Raman scattering (SERS) assay for the quantification of c-MYC in real blood samples. The sensing scheme relies on the use of specifically designed hybrid plasmonic materials and their bioderivatization with a selective peptidic receptor modified with a SERS transducer. Peptide/c-MYC recognition events translate into measurable alterations of the SERS spectra associated with a molecular reorientation of the transducer, in agreement with the surface selection rules. The efficiency of the sensor is demonstrated in cellular lines, healthy donors and a cancer patient.

Silicon particles as trojan horses for potential cancer therapy.

BACKGROUND: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. RESULTS: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. CONCLUSIONS: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.

A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer.

INTRODUCTION: The aim of this study was to compare TOMOX versus FOLFOX4 as first-line treatment of advanced colorectal cancer (CRC). MATERIALS AND METHODS: 191 chemotherapy-naïve patients were randomized to receive TOMOX or FOLFOX4. Patients were evaluated every 3 months and chemotherapy was continued until disease progression or unacceptable toxicity. Overall response rate was the primary endpoint. RESULTS: 183 patients were included in the intent-to-treat analysis (92 TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3 % (p = 0.003) for TOMOX and FOLFOX4, respectively. No statistically significant differences were observed in overall survival (15.6 and 17.2 months; p = 0.475); progression-free survival (7.7 and 8.7 months; p = 0.292), and response duration (6.4 and 7.6 months; p = 0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4 neutropenia (p < 0.0001) and leukopenia (p = 0.028) were more common with the FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group (p = ns). There were two treatment-related deaths in the FOLFOX4 arm and one in the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences between the two regimens for physical and mental composite scores after 6 weeks, and for body pain and emotional role functioning after 6 and 12 weeks; all of these favored the FOLFOX4 arm (p ≤ 0.05). CONCLUSIONS: TOMOX and FOLFOX4 seem to have similar efficacy and are well tolerated in the first-line treatment for advanced CRC with different profiles of toxicity. The convenient TOMOX regimen may offer an alternative to fluoropyrimidine-based regimens.

Aportación de la tomografía por emisión de positrones a la detección y estadificación del cáncer de mama / Contribution of positron emission tomography to the detection and staging of breast cancer

Introducción. La tomografía por emisión de positrones con 18F-fluorodeoxiglucosa (PET-FDG) es una técnica de diagnóstico por la imagen con numerosas aplicaciones en el campo de la oncología. En el cáncer de mama, concretamente, una de sus indicaciones más prometedoras es la estadificación no invasiva, tanto de la afección ganglionar como a distancia, lo cual tendría importantes repercusiones pronósticas y terapéuticas. Material y método. Se ha realizado una revisión de la bibliografía disponible sobre la utilidad de la PETFDG en la detección y estadificación del cáncer de mama. Se incluyen los resultados de la experiencia propia en nuestro centro. Resultados. La PET-FDG tiene especial interés para la detección de tumores en mamas densas, para la determinación de lesiones múltiples y para las mamas protésicas. En la estadificación ganglionar, la PET-FDG presenta una baja sensibilidad, por lo que no puede sustituir el estudio histológico y del ganglio centinela, pero es más exacta que otros métodos no invasivos y es especialmente útil en la valoración de la cadena mamaria interna. En la estadificación a distancia, la PET-FDG puede reemplazar y optimizar otros métodos de imagen habituales, sobre todo en casos de afección locorregional avanzada, elevación de marcadores tumorales y en la caracterización de hallazgos dudosos en la imagen anatómica o gammagráfica. Conclusiones. La PET-FDG tiene un importante impacto en el estudio de extensión del cáncer de mama, y complementa e incluso sustituye la información aportada por otras técnicas diagnósticas; asimismo, modifica el estadio tumoral en un elevado número de pacientes (AU)

Introduction. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is a diagnostic imaging tool with multiple applications in oncology. One of the more promising applications in breast cancer is noninvasive lymph node staging and detection of distant metastases, which may provide useful information about prognosis and treatment response. Material and method. Published studies on FDGPET applications in breast cancer detection and staging were reviewed. We also present our own experience in patients referred for preoperative staging of breast cancer. Results. FDG-PET is very useful in evaluating dense breasts, multicentric disease and breast prostheses. The sensitivity of FDG-PET for nodal staging is low, and consequently it cannot replace either sentinel lymph node biopsy or histologic examination. However, it is more accurate than another noninvasive techniques and is very useful in internal mammary node chain evaluation. FDG-PET can improve and maybe replace conventional imaging in detecting metastatic disease, especially in high risk patients with locoregionally advanced recurrent breast cancer or increased serum tumor markers, and helps to characterize unclear findings of anatomic imaging techniques or scintigraphy. Conclusions. FDG-PET is useful in breast cancer staging. It complements and even improves information from other diagnostic techniques and changes therapeutic management in a high proportion of patients (AU)

[Contribution of positron emission tomography to the detection and staging of breast cancer]. / Aportación de la tomografía por emisión de positrones a la detección y estadificación del cáncer de mama.

INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a diagnostic imaging tool with multiple applications in oncology. One of the more promising applications in breast cancer is noninvasive lymph node staging and detection of distant metastases, which may provide useful information about prognosis and treatment response. MATERIAL AND METHOD: Published studies on FDG-PET applications in breast cancer detection and staging were reviewed. We also present our own experience in patients referred for preoperative staging of breast cancer. RESULTS: FDG-PET is very useful in evaluating dense breasts, multicentric disease and breast prostheses. The sensitivity of FDG-PET for nodal staging is low, and consequently it cannot replace either sentinel lymph node biopsy or histologic examination. However, it is more accurate than another noninvasive techniques and is very useful in internal mammary node chain evaluation. FDG-PET can improve and maybe replace conventional imaging in detecting metastatic disease, especially in high risk patients with locoregionally advanced recurrent breast cancer or increased serum tumor markers, and helps to characterize unclear findings of anatomic imaging techniques or scintigraphy. CONCLUSIONS: FDG-PET is useful in breast cancer staging. It complements and even improves information from other diagnostic techniques and changes therapeutic management in a high proportion of patients.