Small bowel metastasis from embryonal rhabdomyosarcoma of the extremity- a case report.

Rhabdomyosarcoma is the most common soft tissue tumour in children and adolescents, but extremely rare in adults with comparatively worse outcomes. Metastatic disease is not uncommon, but intra-abdominal metastases are exceedingly rare. We report an unusual case of ileal metastases from an upper extremity rhabdomyosarcoma in a 17-year-old male who presented with abdominal pain during a routine follow-up visit. Laparotomy and ileocecectomy for a perforated ileal mass confirmed metastatic embryonal rhabdomyosarcoma with 1 out of 14 positive lymph node metastases. This case demonstrates that, although rare, intra-abdominal metastases should be considered when patients with a rhabdomyosarcoma present with abdominal complaints.

Small bowel metastasis from embryonal rhabdomyosarcoma of the extremity- a case report.

Rhabdomyosarcoma is the most common soft tissue tumour in children and adolescents, but extremely rare in adults with comparatively worse outcomes. Metastatic disease is not uncommon, but intra-abdominal metastases are exceedingly rare. We report an unusual case of ileal metastases from an upper extremity rhabdomyosarcoma in a 17-year-old male who presented with abdominal pain during a routine follow-up visit. Laparotomy and ileocecectomy for a perforated ileal mass confirmed metastatic embryonal rhabdomyosarcoma with 1 out of 14 positive lymph node metastases. This case demonstrates that, although rare, intra-abdominal metastases should be considered when patients with a rhabdomyosarcoma present with abdominal complaints.

Consensus recommendations for optimizing biomarker testing to identify and treat advanced EGFR-mutated non-small-cell lung cancer.

The advent of personalized therapy for non-small-cell lung carcinoma (nsclc) has improved patient outcomes. Selection of appropriate targeted therapy for patients with nsclc now involves testing for multiple biomarkers, including EGFR. EGFR mutation status is required to optimally treat patients with nsclc, and thus timely and accurate biomarker testing is necessary. However, in Canada, there are currently no standardized processes or methods in place to ensure consistent testing implementation. That lack creates challenges in ensuring that all appropriate biomarkers are tested for each patient and that the medical oncologist receives the results for making informed treatment decisions in a timely way. An expert multidisciplinary working group was convened to create consensus recommendations about biomarker testing in advanced nsclc in Canada, with a primary focus on EGFR testing. Recognizing that there are biomarkers beyond EGFR that require timely identification, the expert multidisciplinary working group considered EGFR testing in the broader context of integration into complex lung biomarker testing. Primarily, the panel of experts recommends that all patients with nonsquamous nsclc, regardless of stage, should undergo comprehensive reflex biomarker testing at diagnosis with targeted next-generation sequencing. The panel also considered the EGFR testing algorithm and the challenges associated with the pre-analytic, analytic, and post-analytic elements of testing. Strategies for funding testing by reducing silos of single biomarker testing for EGFR and for optimally implementing the recommendations presented here and educating oncology professionals about them are also discussed.

Multi-frequency detection of a dielectric object using flexible contactless RF sensors for tissue diagnosis.

The aim of this paper is to experimentally assess the capacity of radio-frequency flexible sensors to localize a dielectric object inside a fluid, which could be used as a non contact sensor detected to the detection or the monitoring a local modification of a tissue, such as a tumor or a lesion. The used sensor is an MRI-like antenna, which consists in a flat, flexible and low cost multi-turn split resonator (MTLR), which features a geometrically pre-determined resonance frequency. The MTLR is used here as a transmit and receive sensor monitored by a distant loop coil. The complex impedance changes observed at the ends of the monitoring coil is known to be linked to the dielectric properties of the resonator environment. If a dielectric object is placed close to the resonator, the complex impedance is altered. In this work, an experimental set up is used to assess the relevance of such a measurement scheme to detect the presence of a dielectric inclusion embedded in another dielectric medium. The setup includes a spherical object of 1.5 cm diameter filled with various NaCl solutions moved vertically inside a tank filled with deionized water by means of a three axis robotic arm, to create an electrical conductivity contrast between the inclusion and the media, and three 2 cm diameter MTLR sensors featuring 30, 47 and 70 MHz resonance frequencies, respectively. The sensors are operated through the use of monitoring coils connected to a network analyzer, and measurements are carried out at each position of the spherical object. The resulting sensor responses are plotted and used for the assessment of sensor performances. In addition, a method to combine the multi-frequency data provided by the three different sensors is proposed. Two different metrics regarding the spatial resolution (SR) and the peak signal to noise ratio (PSNR) are computed to characterize the single sensor performances, as well as the enhancement provided by the proposed multi-frequency approach.

Erratum: Therapeutic landscape of metastatic non-small-cell lung cancer in Canada in 2020.

[This corrects the article DOI: 10.3747/co.27.5953.].

Therapeutic landscape of metastatic non-small-cell lung cancer in Canada in 2020.

Lung cancer is the most commonly diagnosed cancer in Canada and remains associated with high mortality. Nevertheless, recent advances in the fields of immuno-oncology and precision medicine have led to significant improvements in clinical outcome in metastatic non-small-cell lung cancer (nsclc). Those improvements were facilitated by a greater understanding of the biologic classification of nsclc, which catalyzed discoveries of novel therapies. Here, we present a comprehensive review of the recent avalanche of practice-changing trials in metastatic nsclc, and we offer an approach to the management of this disease from a Canadian perspective. We begin with an overview of the pathologic and molecular characterization of metastatic nsclc. Next, we review the indications for currently approved immune checkpoint inhibitors, and we provide an approach to the management of disease with a driver mutation. Finally, we address future avenues in both diagnostics and therapeutics for patients with advanced and metastatic nsclc.

Imaging of a dielectric inclusion using a contactless radio-frequency inductive probe for tissue diagnosis.

In this paper, a contactless radio-frequency (RF) inductive probe is used to spatially localize and characterize a complex dielectric organic inclusion in a fluid. The effect of dielectric properties (DP) of this organic material is investigated experimentally and by numerical computations.The used RF probe is a 135 MHz 3 cm diameter and 10 cm long, cylindrical bracelet resonator, placed close to a water tank filled with deionized water which includes a 1.5 cm diameter inclusion filled of air or NaCl solutions and placed in arbitrary positions. The water tank and the inclusion are used to model an organic material including a tumor. The RF probe is used as a transmit and receive sensor. It induces a magnetic field inside the water tank, which, by reciprocity, conveys information about the DP of the investigated material. The impedance changes at the end of the RF probe are directly related to the modifications of the magnetic field, and are measured by means of a network analyzer. A complex fit of the impedance frequency response around the resonance frequency gives access to two quantities proportional to the electrical conductivity and dielectric constant of the inclusion. The inclusion is moved into the water tank along the three axes by means of a robotic arm, so that two three dimensional maps of the equivalent dielectric quantities in function of the inclusion position are sensed by the probe. Then, the inclusion is filled with different conductive NaCl solutions from 0.1 to 1.1 S/m in order to test the ability of the probe to sense the modifications of the dielectric properties of the inclusion. Experimental as well as computation results obtained using the Distributed Point Source Method (DPSM) validate the ability of the proposed probe to localize the inclusion as deep as 1 cm into the water, and the ability of the probe to sense the dielectric property changes of the inclusion.

Bronchoalveolar lavage fluid neutrophilia is associated with the severity of pulmonary lesions during equine asthma exacerbations.

BACKGROUND: The severe form of equine asthma is associated with pathological changes of the peripheral airways and pulmonary parenchyma that are only partly described. Also, the relationship between these structural alterations and the percentage of neutrophils found within the airway lumen, assessed by bronchoalveolar lavage fluid (BALF) cytology, remains ill-defined. OBJECTIVE: To examine the histological lesions associated with equine asthma during disease exacerbation and remission, and their relationship with lung function and BALF neutrophilia. STUDY DESIGN: Observational retrospective study. METHODS: Peripheral lung tissues, BALF cytology and lung function data from 61 horses (22 controls, 24 asthma exacerbations and 15 asthma remission) were obtained from an equine pulmonary tissue bank. Two pathologists semi-quantitatively assessed histological features, including airway wall inflammation, interstitial fibrosis, mucus cell hyperplasia, mucostasis, peribronchiolar metaplasia, presence of granuloma and the overall severity of these lesions. RESULTS: Mucostasis, mucus cell hyperplasia, peribronchiolar metaplasia and interstitial fibrosis were associated with disease exacerbation (P≤0.05), and these changes were all attenuated during remission. Airway wall inflammation was greater in horses with asthma in exacerbation compared with horses with asthma in remission and control horses (P≤0.05). Acute (neutrophilic) airway wall inflammation was more frequently detected in asthmatic cases compared with control horses (P<0.0001) and was associated with BALF neutrophilia >5% in control horses (P = 0.002). The degree of bronchiolar inflammation was higher in asthmatic horses in remission stabled and treated pharmacologically compared with those kept on pasture (P = 0.04). MAIN LIMITATIONS: Samples obtained from a convenient cohort of horses were studied. CONCLUSIONS: Severely asthmatic horses present parenchymal and peribronchial/peribronchiolar lesions possibly contributing to the obstructive nature of the disease.

Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses.

BACKGROUND: Remodeling of the peripheral airways persists during the asymptomatic phase of heaves. Assessing the histology of large bronchi could facilitate the diagnosis of heaves during remission of the disease. HYPOTHESIS: Airway inflammation and remodeling in endobronchial biopsy (EBB) specimens differentiate horses with heaves from controls, independently of their clinical status (exacerbation or remission). ANIMALS: Fourteen healthy horses and 24 horses with heaves. METHODS: A 14-point scoring system assessing central bronchial wall inflammation and remodeling was developed. The score was validated by 2 pathologists using specimens obtained from 18 horses (6 controls, 6 with heaves exacerbation, and 6 with heaves remission) in which lung function had been assessed with impulse oscillometry. Clinical and research application of the score was evaluated using biopsy specimens obtained from 20 additional horses (8 controls, 6 with heaves exacerbation, and 6 with heaves remission). RESULTS: The score was repeatable (interclass correlation coefficient = 69%). It differentiated horses with heaves in exacerbation (mean ± SD: 6.2 ± 2.2) from those in remission (4.0 ± 1.0) and controls (3.6 ± 1.7, P < 0.0001). The histological scores of horses with heaves correlated with the ratio of respiratory resistance (R) at 5 and 10 Hz (R5 : R10 ratio, r = 0.65, P = 0.03), a parameter assessing airway obstruction. CONCLUSIONS AND CLINICAL SIGNIFICANCE: The proposed histological scoring system correlates with the degree of airway obstruction measured by impulse oscillometry. However, it does not discriminate horses with heaves in remission from controls. Evaluation of EBB specimens might be considered in future research and clinical studies of respiratory diseases in horses.

Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers.

BACKGROUND: RET rearrangements are targetable, oncogenic lung cancer drivers. While previous series have shown durable clinical benefit with pemetrexed-based therapies in ALK- and ROS1-rearranged lung cancers, the benefits of pemetrexed-based treatments in patients with RET-rearranged lung cancers relative to other genomic subsets have not previously been explored. PATIENTS AND METHODS: A retrospective review of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas and evidence of a RET, ROS1, or ALK rearrangement, or a KRAS mutation was conducted. Patients were eligible if they received treatment with pemetrexed alone or in combination. The primary outcome of progression-free survival (PFS), and secondary outcomes of overall response rate (ORR, RECIST v1.1), time to progression (TTP), and time to treatment discontinuation were compared between RET-rearranged and groups of ROS1-rearranged, ALK-rearranged, and KRAS-mutant lung cancers. RESULTS: We evaluated 104 patients. Patients with RET-rearranged lung cancers (n = 18) had a median PFS of 19 months [95% confidence interval (CI) 12-not reached (NR)] that was comparable with patients with ROS1- (23 months, 95% CI 14-NR, n = 10) and ALK-rearranged (19 months, 95% CI 15-36, n = 36) lung cancers, and significantly improved compared with patients with KRAS-mutant lung cancers (6 months, 95% CI 5-9, P < 0.001, n = 40). ORR (45%), median TTP (20 months, 95% CI 17-NR), and median time to treatment discontinuation (21 months, 95% CI 6-NR) in patients with RET-rearranged lung cancers were not significantly different compared with patients with ALK- and ROS1-rearranged lung cancers, and improved compared with patients with KRAS-mutant lung cancers. CONCLUSION: Durable benefits with pemetrexed-based therapies in RET-rearranged lung cancers are comparable with ALK- and ROS1-rearranged lung cancers. When selecting therapies for patients with RET-rearranged lung cancers, pemetrexed-containing regimens should be considered.

Expression and regulation of CCL15 by human airway smooth muscle cells.

BACKGROUND: Structural cells are an important reservoir of chemokines that coordinate the influx of various immune cells to the lungs of asthmatics. Airway smooth muscle cells (ASMC) are an important source of these chemokines. CCL15 is a recently described chemo-attractant for neutrophils, eosinophils, monocytes and lymphocytes. OBJECTIVE: To determine the production and the regulation of CCL15 by ASMC and to investigate its production in asthmatic airways. METHODS: Human ASMC were obtained from main bronchial airway segments of patients with mild, moderate and severe asthma. To induce chemokine production, cells were incubated with IL-4, IL-13, TNF-α or IFN-γ in presence or absence of dexamethasone, mithramycin A (SP-1 inhibitor) or the IKK-2 inhibitor, AS602868. CCL15 mRNA expression was evaluated by real-time PCR. Immunoreactive CCL15 was detected by immuno-fluorescence and CCL15 protein concentration in the supernatant was measured using ELISA. RESULTS: CCL15 is constitutively expressed in human ASMC and is strongly up-regulated by TNF-α. This up-regulation is inhibited by dexamethasone, mithramycin A and AS602868. TNF-α-induced CCL15 levels can be synergistically enhanced by the presence of IFN-γ, at both the transcriptional and translation level. This synergism is NF-κB-dependent. Asthmatic biopsies demonstrated higher expression of CCL15 compared with non-asthmatic controls. CONCLUSION AND CLINICAL RELEVANCE: Our results show that ASMC are a potent source of CCL15 in the airways and may directly participate in the recruitment of inflammatory cells to asthmatic airways. Targeting the production of CCL15 by ASMC might reduce the inflammatory response within the airways of asthmatic patients.

Local and systemic effects of Na+/K+ATPase inhibition.

The positive inotropic and electrophysiological effects of cardiac glycosides on cardiac muscle are mediated through inhibition of Na+/K+ ATPase by binding to a specific extracytoplasmic site of the a-subunit of this enzyme. The inhibition of Na+/K+ ATPase affects ionic flux and produces direct local effects on cardiac contractility, electrical excitability and conduction, but also profound systemic effects mainly as a result of haemodynamic changes. These effects are responsible for beneficial therapeutic as well as toxic effects. Inhibition of Na+/K+ ATPase results in potentiation of K+ loss from cells and Na+ entry into cells, so consequently affects action potential generation and propagation. This also underlines the potentiation of certain effects of cardiac glycosides by hypokalemia and hypomagnesaemia, and the effects of changes in calcium homeostasis on the cardiac glycoside pharmacodynamics. Furthermore, inhibition of Na+/Ca++ exchange enhances Ca++ mobilization and promotes contractility. These effects (locally and systemically) differ greatly, depending on the haemodynamic status and myocardial oxygen supply. Cardiac glycosides have less affinity for Na+/K+ ATPases at other sites (e.g. skeletal muscle), but some extracardiac effects (vascular effects, effects on colour vision, CNS and autonomic effects, renal effects) may be related to Na+/K+ ATPase inhibition.

Identification of a new cleavage site of the 3C-like protease of rabbit haemorrhagic disease virus.

The calicivirus rabbit haemorrhagic disease virus (RHDV) possesses a 3C-like protease which processes the RHDV polyprotein. In order to monitor the proteolytic activity of the RHDV 3C-like protease on its putative target sequences, i.e. the 10 EG dipeptide bonds distributed along the large polyprotein, a new approach was carried out. Preliminary experiments showed that the luciferase gene when fused in-frame with a long gene yielded a fusion protein almost devoid of luciferase activity. This reporter system was used to test which EG dipeptide bonds were cleaved by the RHDV protease when the coding sequences of the dipeptides and their flanking sequences were inserted at the junction between the protease and luciferase genes. The coding sequences of the fusion proteins were cloned downstream of the T7 promoter and the proteolytic activity was evaluated by measuring the luciferase activity in both in vitro and 'in vivo' systems. The EG dipeptide bonds at positions 718-719, 1108-1109 and 1767-1768 were confirmed as cleavage sites and a new cleavage site EG (143-144) was identified.

Epidemiology and control of schistosomiasis mansoni in communities living on the Cuando River floodplain of East Caprivi, Namibia.

The Cuando River area of eastern Caprivi, Namibia, is highly endemic for Schistosoma mansoni whereas S. haematobium transmission, due to the scarcity of its intermediate host snail, Bulinus africanus, does not occur. Chemotherapy (6-monthly blanket treatments with praziquantel) combined with focal mollusciciding (monthly application of niclosamide) was used in a project in the area to control the disease. Although as many adults and pre-school children as possible were tested and treated, the project concentrated largely on school-age children. It took 3 years for prevalence to decline from > 80% to 20% because of a lack of proper sanitary facilities and piped water supplies and high rates of absenteeism and re-infection. However, intensity of infection decreased more rapidly, from an arithmetic mean of > 200 to < 5 eggs/g faeces. Hepatomegaly was common among school children when the project started but could be seen in only a small percentage of them after 3 years of control. Neither the bovine schistosome, S. mattheei, nor the lechwe schistosomes, S. margrebowiei and S. leiperi, were observed in the excreta of humans living in the area.

[Diagnosis and evaluation of spread of prostate cancer]. / Diagnostic et bilan d'extension du cancer de la prostate.

In more than 50% of the cases, the diagnosis of prostate cancer is made at the time of extra-prostatic or distant disease involving poor prognosis for cure. Small tumours for which curative treatment is possible are asymptomatic. Thus, useful early diagnosis of prostatic cancer is based on digital rectal examination and PSA concentration. PSA levels are also indicative of tumour volume. Thus, determining dissemination becomes significant only in the case of elevated PSA, indicating a large tumour.

Thermoregulation during transurethral microwave thermotherapy: experimental and clinical fundamentals.

Transurethral microwave thermotherapy of 340 patients treated at our center for benign prostatic hypertrophy shows the importance of the role played by two thermoregulation processes during the procedure. The first one is artificial and automatically driven by the machine (the power output and cooling rate are adjusted to the urethral and rectal temperature safety thresholds). The second one is natural thermoregulation; the latter is species specific, organ specific, zone specific and even cell specific. Thermoregulation variability is linked to the geometry of the gland, vessel distribution, histology and tissue conductivity. This variability has been demonstrated by interstitial thermometry and histological study. Interstitial thermometry was performed during treatment in 30 dogs and 35 patients; a histological study of prostate specimens was performed 1-12 weeks after treatment in 30 dogs and 15 patients. The human prostate is more resistant to heat than the dog prostate of a comparable volume and treated with the same thermal dose. The prostate of a young patient requires a higher thermal dose than that of an old patient with the same prostate volume in order to achieve a comparable intraprostatic temperature, probably due to a more viable blood supply. The transition zone is more sensitive to heat than the peripheral zone, as demonstrated by temperatures recorded at the same distance from the antenna of up to 60 versus 42 degrees C, respectively. Acinar cells seem to be more resistant to heat than smooth muscle cells when exposed to the same temperature level, as demonstrated by microscopic examination at the periphery of the treated area.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural tube defect etiology: new evidence concerning maternal hyperthermia, health and diet.

The authors conducted a retrospective case-control study to determine risk factors for neural tube defects (NTD). 88 Louisiana women (44 matched pairs) were interviewed. Previous evidence suggested that maternal health and/or nutrition may be involved in the etiology of NTD. The findings substantiate the importance of maternal risk factors, including the apparent elevation of body temperature from taking hot baths during the first gestational month. Maternal health, as measured by reported illness and use of medications during pregnancy, was also significant. Several dietary factors, including intake of foods high in beta carotene, appeared to confer a protective effect. These findings suggest that some risk factors, particularly those involving maternal nutrition, may be population-specific.

Altered tobramycin pharmacokinetics during chemoprophylaxis in bladder surgery.

The effect of bladder surgery on the pharmacokinetics of tobramycin in hospitalized patients was studied. Fourteen patients with vesical neoplasia undergoing urinary tract surgery were given tobramycin in a dose of 2 mg/kg of body weight. Each patient received the dose at the induction of anesthesia, about 1 h before surgical incision. For seven patients, the drug was also administered 3 weeks later when nutritional conditions were normal. The pharmacokinetic parameters were determined by a two-compartment open model. Except for renal clearance, no significant difference appeared between pharmacokinetic parameters determined from serum data during peri- and postoperative periods. During this work, tobramycin excretion in urine was studied. Twenty-four hours after drug administration, the mean urine tobramycin levels were 25.5 +/- 9.06 and 41.6 +/- 21.5 micrograms/ml after peri- and postoperative administration, respectively; these values were higher than the MICs for most urinary tract pathogens. Seventy-two hours after perioperative administration, the mean value was still elevated (3.54 micrograms/ml), but 72 h after postoperative administration, the urinary tobramycin concentration was not detectable. The percentages of tobramycin recovered unchanged in urine were 54 and 79% after peri- and postoperative administration, respectively. When tobramycin was administered during surgery, a long terminal log-linear phase, with a mean half-life of 25.6 h, was detected. The ratio of renal clearance to total body clearance was 0.52 and 0.79 after peri- and postoperative administration, respectively.