The combination cytology/epichek test in non muscle invasive bladder carcinoma follow-up: Effective tool or useless expence?

ObjectiveTo identify in which cases after cytological diagnosis, the Bladder EpiCheck test could represent an effective tool in non-muscle invasive bladder carcinoma or an useless expence.Materials and methods375 patients diagnosed with non-muscle invasive bladder cancer, 269 with high grade urothelial carcinoma and 106 with carcinoma in situ, were treated and followed for 1 year. The treatment was an intravesical instillation of Bacillus Calmette-Guerin in 305 patients and Mitomycin-C in 70 patients.During the follow-up patients were evaluated by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. Bladder EpiCheck test was performed together with cytology in all cases.ResultsAnalyzing Bladder Epicheck results for each category defined by the Paris System for Reporting Urinary Cytology, we found that the Episcore >60 correlates with histological diagnosis of high grade urothelial carcinoma (HGUC) in atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma (P = 0.0002 Odds Ratio 0.05926 95% Confidence Interval from 0.01127 to 0.3116 and P = 0.0009 Odds Ratio 0.0315595% Confidence Interval from 0.001683 to 0.5914, Fisher's exact test, respectively), while in Negative for high grade urothelial carcinoma and HGUC patients Episcore is not helpful to identify cases with histological diagnosis of HGUC (P = 0.101 and P = 0.58 Fisher's exact test, respectively). Considering an Episcore ≥ 90 in the HGUC cytological group, this seems not to be correlated with a histological diagnosis of HGUC (P = 0.090 Fisher's exact test).ConclusionsCytology and Bladder EpiCheck test in combination may have the potential to reduce cystoscopies in the follow-up of non-muscle invasive bladder cancer only for cytological diagnoses of atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma . Moreover, in patients with a cytological diagnosis of Negative for high grade urothelial carcinoma or HGUC, cytology alone seems to be safe and cost-effective.     

Range of motion of foot joints following total ankle replacement and subtalar fusion

BackgroundIn severe cases of ankle and subtalar arthritis, arthrodesis of the subtalar joint is performed in combination with ankle arthroplasty. In these special cases gait analysis reveals real motion at the replaced tibiotalar joint.MethodsTwenty-three patients affected by ankle and subtalar arthritis, treated either with a 3-component or a 2-component prosthesis in combination with subtalar arthrodesis, were clinically evaluated preoperatively and at a minimum of 1-year follow-up. Gait analysis was performed postoperatively using a multi-segment foot protocol. Foot kinematics were compared to corresponding data from a healthy control group.ResultsClinical scores significantly improved from preoperative to follow-up. The clinically measured passive ankle dorsiflexion/plantarflexion significantly improved at the follow-up. Patients’ normalized walking speed and stride length were significantly lower than those in control. With exception of the ankle frontal-plane motion, sagittal-plane mobility of foot joints was about 50% than that in healthy joints.ConclusionsImprovement in clinical scores was found for both prostheses. Normal spatio-temporal parameters were not restored. In these patients, fusion of the subtalar joint appeared to be compensated by larger frontal-plane motion at the tibiotalar joint.Level of evidenceLevel III- retrospective comparative study.The study was approved by the local Ethics Committee as protocol MAT (protocol registration at clinicaltrials.gov NCT03356951).     

Developmental dysplasia of the hip screening during the lockdown for COVID-19: experience from Northern Italy

PurposeDevelopmental dysplasia of the hip (DDH) ultrasound screening (USS), which is usually performed in Italy as an outpatient, was halted for an indefinite period in most centres during lockdown. The aim of this study was to analyze the effect of COVID-19 on DDH-USS, in two paediatric orthopaedic centres in one of the most critical areas of the western World.MethodsAn academic teaching hospital and paediatric trauma centre (T) and a University hospital and DDH referral centre (H), classified as national COVID-19 hubs, were involved. Graf’s method was applied in both centres. In T, paediatricians directly referred only patients with delayed DDH-USS or suspicious unstable hips; in H, paediatricians or parents could directly refer to the screening service.ResultsThe mean age of the 95 patients (190 hips) who were referred for DDH-USS in T, was 3.85 months (0.1 to 7.4); 175 were type I, nine were type IIa (+ and -), five type D and one type IV. In H, the screened patients in 2020 were only 78% of the same period in 2019. A total of 28 patients with 32 hips (8 IIb, 5 IIc, 8 D, 11 III) had late diagnosis at a mean age of 114 days (96 to 146). In the same period in 2019 only eight patients with 11 hips (8 IIb, 1 D, 1 III, 1 IV) at a mean age of 142 days (92 to 305) had late diagnosis.ConclusionDDH-USS was the only screening in newborns which halted during lockdown. Few centres, which still performed diagnosis and treatment, were overloaded causing a delay in DDH management.Level of evidenceIV.     

Technical basis for magnetic resonance images

The spin-echo procedure is the basic technique in a magnetic resonance (MR) study (the magnetization vector is flipped by 90° onto the ortogonal plane to the main magnetic field). Very soon after the MR procedure was developed, it was pointed out how important it is to achieve the needed contrast with shorter repetition times (TRs) to reduce the imaging time. Recently, fast imaging techniques have been introduced (partial flip angles, short TRs, and the lack of 180° radiofrequency pulses to refocus the spins are their main characteristics; the spins are refocused by the application of a gradient reversal technique). These techniques are particularly needed in pediatric neuroradiology, where the examination time must be as short as possible. At present, partial flip-angle techniques are almost completely replacing the conventional spin-echo procedure, but the variations in flip angle could result in a change in contrast. For these reasons, conventional spin-echo techniques may still be useful in a routine MR study.Presented at the 11th Meeting of the European Society for Paediatric Neurosurgery, Naples 1988     

Thyroid carcinoma mimicking a toxic adenoma

A young woman with a thyroid papillary carcinoma behaving as an autonomously hyperfunctioning nodule is described. Only 17 similar patients have been seen in the past 25 years. It is emphasized that hyperthyroidism does not exclude malignant disease in hot nodules. This possibility suggests that all thyroid nodules, either cold or hot, require careful management. Therefore, in at risk cases, surgery could be the most useful treatment.     

Serotonergic inhibition of the mossy fibre—granule cell glutamate transmission in rat cerebellar slices

Summary The glutamatergic mossy fibre granule cell pathway has been investigated in rat cerebellar slices. Exposure to 35 mM KCI, a concentration of K⁺ known to elicit Ca²⁺-dependent releases of excitatory amino acids from cerebellar slices, raised cGMP levels. The cGMP response was decreased in a concentration-dependent manner by D-(–)-2-amino-5-phosphonopentanoic acid (D-AP5) and by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) indicating the involvement of ionotropic glutamate receptors of both the N-methyl-D-aspartate (NMDA) and the non-NMDA type. The K⁺-evoked production of cGMP was potently inhibited (EC₅₀ = 1.21 nM) by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT₂ receptor agonist. The effect of DOI (0.01 M) was antagonized by 0.03 M of the 5-HT₂ receptor antagonists ketanserin and methiothepin. At concentrations higher than 0.1 M, both antagonists increased on their own the cGMP response elicited by high-K⁺. This effect was insensitive to tetrodotoxin.It had been previously shown that rat mossy fibre endings release glutamate upon depolarization and that such release can be inhibited by activation of 5-HT₂ receptors sited on the mossy fibre endings. Altogether the available data suggest the following conclusions: (a) the glutamate/aspartate endogenously released in cerebellar slices during K⁺ depolarization increase cGMP synthesis through the activation of both NMDA and non-NMDA receptors; (b) a portion of the cGMP response can be prevented by 5-HT₂ receptor activation and may reflect the activity of the mossy fibre-granule cell pathway. Thus serotonin is likely to exert a potent inhibitory control of the excitatory mossy fibre input to the cerebellum by acting at receptors of the 5-HT₂ type. Correspondence to M. Raiteri at the above address     

Pharmacokinetics of 4-demethoxydaunorubicin in cancer patients

Summary The clinical pharmacokinetics of 4-demethoxydaunorubicin was investigated in 28 cancer patients who received the drug orally. The majority of the patients were elderly (median age, 72 years). Nine of them also received an i. v. dose, and the bioavailability of the oral dose ranged between 9% and 39%. 4-Demethoxydaunorubicin peak levels were achieved 2–4 h after the oral dose in most patients. The drug was rapidly and extensively metabolized to 4-demethoxy-13-hydroxydaunorubicin, which is probably as active as the parent drug. The metabolite levels were much higher and longer lasting than the parent drug, suggesting that it may play an important role in the drug's pharmacological effects.     

Isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine-activated killer cells in the treatment of in-transit metastases from limb cutaneous melanoma

Background: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy. Methods: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9–12 × 10⁶ IU/M²/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8–28 × 10⁹) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9–12×10⁶ IU/m²/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP. Results: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Conclusions: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment.     

Interethnic and interindividual variabilities of platelet sulfotransferases activity in Italians and Finns

Objective: The aim of this investigation was to see whether there was interethnic variability in the platelet activities of catechol- and phenol sulfotransferases in Italians and Finns. Methods: The activities of catechol- and phenol sulfotransferases were measured in platelets obtained from 103 Italian and 74 Finnish individuals. Blood donors were obtained from healthy volunteers free from drugs and without apparent disease. The activities of catechol- and phenol sulfotransferases were measured with 60 μM dopamine and 4 μM 4-nitrophenol as substrates, respectively Results: The activity of catechol sulfotransferase was not gender dependent and the median estimates (pmol/min/mg) were 9.10 in Italians and 6.37 in Finns (P = 0.0018). The activity of phenol sulfotransferase activity was gender dependent in Finns but not in Italians. The median estimates (pmol/min/mg) were 3.81 in Finnish men and 1.18 in Finnish women (P = 0.0007). In Italian men and women, the median estimates (pmol/min/mg) of phenol sulfotransferase activity were 1.25 and 1.24, respectively (NS). Conclusion: This study shows that platelet catechol sulfotransferase activity is greater in Italians than Finns and that the activity of phenol sulfotransferase is gender regulated in Finns but not in Italians. Thus, interethnic differences exist in platelet sulfotransferases between Italians and Finns. Received: 16 April 1999 / Accepted in revised form: 20 August 1999