Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non-muscle-invasive bladder cancer?

OBJECTIVES To prospectively evaluate the outcome of combined microwave-induced bladder wall hyperthermia and intravesical mitomycin C instillation (thermochemotherapy) in patients with recurrent non-muscle-invasive bladder cancer. METHODS Between 2003 and 2009, 21 patients (median age 70 years, range 35-95 years) with recurrent non-muscle-invasive bladder cancer (pTaG1-2 n = 9; pTaG3 n = 3; pT1 n = 9; concurrent pTis n = 8) were prospectively enrolled. Of 21 patients, 15 (71%) had received previous intravesical instillations with bacillus Calmette-Guérin, mitomycin C and/or farmorubicin. Thermochemotherapy using the Synergo system was carried out in 11 of 21 patients (52%) with curative intent, and in 10 of 21 patients (48%) as prophylaxis against recurrence. RESULTS The median number of thermochemotherapy cycles per patient was six (range 1-12). Adverse effects were frequent and severe: urinary urgency/frequency in 11 of 21 patients (52%), pain in eight of 21 patients (38%) and gross hematuria in five of 21 patients (24%). In eight of 21 patients (38%), thermochemotherapy had to be abandoned because of the severity of the adverse effects (pain in 3/8, severe bladder spasms in 2/8, allergic reaction in 2/8, urethral perforation in 1/8). Overall, six of 21 patients (29%) remained free of tumor after a median follow up of 50 months (range 1-120), six of 21 patients (29%) had to undergo cystectomy because of multifocal recurrences or cancer progression and seven of 21 patients (33%) died (2/7 of metastatic disease, 5/7 of non-cancer related causes). CONCLUSIONS Given the high rate of severe side-effects leading to treatment discontinuation, as well as the limited tumor response, thermochemotherapy should be offered only in highly selected cases of recurrent non-muscle-invasive bladder cancer.

FGFR3 expression in primary invasive bladder cancers and matched lymph node metastases

PURPOSE FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic therapies. We assessed FGFR3 protein expression in primary bladder tumors and matched nodal metastases. MATERIALS AND METHODS We examined matched primary tumor and nodal metastases from 150 patients with bladder cancer clinically staged as N0M0. Four samples per patient were incorporated into a tissue microarray and FGFR3 expression was assessed by immunohistochemistry. FGFR3 expression was tested for an association with categorical clinical data using the Fisher exact test, and with overall and recurrence-free survival by Kaplan-Meier analysis. RESULTS Duplicate spots from primary tumors and lymph node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p <0.001). Overall FGFR protein expression levels did not differ between primary and metastatic lesions (p = 0.78). Up-regulated expression was recorded in 53 of 106 evaluable primary tumor spots and 56 matched metastases. Concordance of FGFR3 expression levels in 79 matched primary tumor and metastasis specimens was high (OR 8.45, p <0.001). In 15 and 12 patients expression was up-regulated in only metastasis and in only the primary tumor, respectively. Overall and recurrence-free survival was not related to FGFR3 expression. CONCLUSIONS FGFR3 expression in matched primary and metastasized bladder cancer specimens showed good but not absolute concordance. Thus, in most patients primary tumor FGFR3 status can guide the selection of FGFR targeted therapy.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients

BACKGROUND The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

The relative importance of immediate allelopathy and allelopathic legacy in invasive plant species

Abstract Some introduced invasive species may be competitively superior to natives because they release allelochemicals, which negatively affect native species. Allelochemicals can be immediately effective after being released but can also persist in soils, resulting in a legacy effect. However, to our knowledge there are no studies which distinguish between allelopathic legacy and immediate allelopathy of invasive species and also test for their relative importance and possible interdependence. We used eleven invasive species and tested whether they show immediate allelopathy and allelopathic legacy effects in a factorial pairwise competition experiment using field-collected soil (invaded/non-invaded) and activated carbon to neutralize allelochemicals. We grew two native and the invasive species in both monocultures and pairwise mixtures. In monocultures, the native species did not experience an allelopathic legacy effect of the invasives, suggesting that invaders generally lack persistent allelochemicals. However, the effects of invader allelochemicals were modulated by competitive interactions. In competition, immediate allelopathy decreased competitive ability of natives, while allelopathic legacy positively affected the natives. Moreover, immediate allelopathic and allelopathic legacy effects were strongly negatively correlated. Our results suggest that both immediately released allelochemicals and the allelochemical legacy of invasive species are important for plant performance under natural conditions, and that natives should be able to recover once the invaders are removed. To test whether immediate allelopathy is responsible for plant invasion success, further studies should compare allelopathic effects between invasive and closely related native species.

Mechatronic feasibility of minimally invasive, atraumatic cochleostomy

Robotic assistance in the context of lateral skull base surgery, particularly during cochlear implantation procedures, has been the subject of considerable research over the last decade. The use of robotics during these procedures has the potential to provide significant benefits to the patient by reducing invasiveness when gaining access to the cochlea, as well as reducing intracochlear trauma when performing a cochleostomy. Presented herein is preliminary work on the combination of two robotic systems for reducing invasiveness and trauma in cochlear implantation procedures. A robotic system for minimally invasive inner ear access was combined with a smart drilling tool for robust and safe cochleostomy; evaluation was completed on a single human cadaver specimen. Access to the middle ear was successfully achieved through the facial recess without damage to surrounding anatomical structures; cochleostomy was completed at the planned position with the endosteum remaining intact after drilling as confirmed by microscope evaluation.

CT coronary angiography versus conventional invasive coronary angiography - the view of the referring physician

PURPOSE Assessment of experience gained by local referring physicians with the procedure of coronary computed tomographic angiography (CCTA) in the everyday clinical routine. MATERIALS AND METHODS A 25-item questionnaire was sent to 179 physicians, who together had referred a total of 1986 patients for CCTA. They were asked about their experience to date with CCTA, the indications for coronary imaging, and their practice in referring patients for noninvasive CCTA or invasive catheter angiography. RESULTS 53 questionnaires (30 %) were assessable, corresponding to more than 72 % of the patients referred. Of the referring physicians who responded, 94 % saw a concrete advantage of CCTA in the treatment of patients, whereby 87 % were 'satisfied' or 'very satisfied' with the reporting. For excluding coronary heart disease (CHD) where there was a low pre-test probability of disease, the physicians considered CCTA to be superior to conventional coronary diagnosis (4.2 on a scale of 1 - 5) and vice versa for acute coronary syndrome (1.6 of 5). The main reasons for unsuitability of CCTA for CT diagnosis were claustrophobia and the absence of a sinus rhythm. The level of exposure to radiation in CCTA was estimated correctly by only 42 % of the referring physicians. 90 % of the physicians reported that their patients evaluated their coronary CT overall as 'positive' or 'neutral', while 87 % of the physicians whose patients had undergone both procedures reported that the patients had experienced CCTA as the less disagreeable of the two. CONCLUSION CCTA is accepted by the referring physicians as an alternative imaging procedure for the exclusion of CHD and received a predominantly positive assessment from both the referring physicians and the patients.

Response to neoadjuvant treatment of invasive ductal breast carcinomas including outcome evaluation: MRI analysis by an automatic CAD system in comparison to visual evaluation

BACKGROUND The aim of this study was to evaluate imaging-based response to standardized neoadjuvant chemotherapy (NACT) regimen by dynamic contrast-enhanced magnetic resonance mammography (DCE-MRM), whereas MR images were analyzed by an automatic computer-assisted diagnosis (CAD) system in comparison to visual evaluation. MRI findings were correlated with histopathologic response to NACT and also with the occurrence of metastases in a follow-up analysis. PATIENTS AND METHODS Fifty-four patients with invasive ductal breast carcinomas received two identical MRI examinations (before and after NACT; 1.5T, contrast medium gadoteric acid). Pre-therapeutic images were compared with post-therapeutic examinations by CAD and two blinded human observers, considering morphologic and dynamic MRI parameters as well as tumor size measurements. Imaging-assessed response to NACT was compared with histopathologically verified response. All clinical, histopathologic, and DCE-MRM parameters were correlated with the occurrence of distant metastases. RESULTS Initial and post-initial dynamic parameters significantly changed between pre- and post-therapeutic DCE-MRM. Visually evaluated DCE-MRM revealed sensitivity of 85.7%, specificity of 91.7%, and diagnostic accuracy of 87.0% in evaluating the response to NACT compared to histopathology. CAD analysis led to more false-negative findings (37.0%) compared to visual evaluation (11.1%), resulting in sensitivity of 52.4%, specificity of 100.0%, and diagnostic accuracy of 63.0%. The following dynamic MRI parameters showed significant associations to occurring metastases: Post-initial curve type before NACT (entire lesions, calculated by CAD) and post-initial curve type of the most enhancing tumor parts after NACT (calculated by CAD and manually). CONCLUSIONS In the accurate evaluation of response to neoadjuvant treatment, CAD systems can provide useful additional information due to the high specificity; however, they cannot replace visual imaging evaluation. Besides traditional prognostic factors, contrast medium-induced dynamic MRI parameters reveal significant associations to patient outcome, i.e. occurrence of distant metastases.

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.

BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING The Medicines Company and Terumo.

Minimally invasive surgery technique for re-enclavation of prepupillary iris-claw IOLs

BACKGROUND Disenclavation is a common complication of prepupillary iris-claw intraocular lenses (IOL). We present a new minimally invasive revision surgery technique for reenclavation of prepupillary iris-claw IOLs using standard 23 Gauge (G) vitrectomy instruments. HISTORY AND SIGNS Three cases of revision surgery by unilaterally dislocated prepupillary iris-claw IOLs are presented. THERAPY AND OUTCOME Two 20 G sideports 90 degrees apart were constructed. Healon 10® was injected to maintain the anterior chamber. A standard enclavation needle was introduced to rotate the optic into correct position and a 23 G endgrasping forceps was used to grasp and stabilize the IOL for enclavation. The reenclavation was successful in all three cases and the mean visual acuity improved from preoperatively 0.1 (range counting fingers [CF] to 0.25) to 0.6 (range 0.4 to 0.8) with no significant induction of astigmatism. CONCLUSIONS This minimally invasive reenclavation technique for repositioning of the prepupillary iris claw IOL appears to lead to successful and rapid visual rehabilitation.

Non-invasive hemodynamic monitoring in trauma patients.

BACKGROUND The assessment of hemodynamic status is a crucial task in the initial evaluation of trauma patients. However, blood pressure and heart rate are often misleading, as multiple variables may impact these conventional parameters. More reliable methods such as pulmonary artery thermodilution for cardiac output measuring would be necessary, but its applicability in the Emergency Department is questionable due to their invasive nature. Non-invasive cardiac output monitoring devices may be a feasible alternative. METHODS A systematic literature review was conducted. Only studies that explicitly investigated non-invasive hemodynamic monitoring devices in trauma patients were considered. RESULTS A total of 7 studies were identified as suitable and were included into this review. These studies evaluated in a total of 1,197 trauma patients the accuracy of non-invasive hemodynamic monitoring devices by comparing measurements to pulmonary artery thermodilution, which is the gold standard for cardiac output measuring. The correlation coefficients r between the two methods ranged from 0.79 to 0.92. Bias and precision analysis ranged from -0.02 +/- 0.78 l/min/m(2) to -0.14 +/- 0.73 l/min/m(2). Additionally, data on practicality, limitations and clinical impact of the devices were collected. CONCLUSION The accuracy of non-invasive cardiac output monitoring devices in trauma patients is broadly satisfactory. As the devices can be applied very early in the shock room or even preclinically, hemodynamic shock may be recognized much earlier and therapeutic interventions could be applied more rapidly and more adequately. The devices can be used in the daily routine of a busy ED, as they are non-invasive and easy to master.