A narrative review of individualized treatments of genitourinary tumors: is the future brighter with molecular evaluations?

Few molecular prognostic and predictive biomarkers have been identified so far in genitourinary tumors. We started from a literature search to explore the status of the art of molecular pathology tests as diagnostic, prognostic, predictive biomarkers in genitourinary cancers. Next generation sequencing approaches now provide mind-changing information in the fields of kidney cancer diagnosis, predictive oncology of urothelial cancer, understanding the causes of testicular and penile cancer, and the comprehension of the drivers of prostate cancer progression beyond androgen regulation. The classification of kidney cancer will be based soon on molecular changes. The causes of non-HPV related penile cancer are largely unknown. The emerging high incidence of testicular cancer could be explained only on the basis of molecular changes. The response to novel therapeutic agents in prostatic and urothelial cancer will require thorough molecular tumor characterization. The hereditary risk of patients with early onset prostate cancer and their potential treatment with targeted therapy requires germline and somatic genetic assays. The implementation of effective biomarkers for the response to immune check-point inhibitors in genitourinary cancer is based on the assessment of inflammatory expression profiles and the tumor mutational burden. This review deals with the current tests and provides a tentative foresee of the future molecular biomarkers of genitourinary cancer.     

Light reflection rheography and thoracic outlet syndrome

The authors have studied with a light reflection rheograph (LRR) 112 cases: 54 patients with suspected "thoracic outlet syndrome" (TOS) in the functional phase, 28 patients with phlebothrombosis localized in upper limbs, and a control group of 30 healthy subjects to evaluate the upper limbs' venous outlet. They recorded a good correlation among results obtained with LRR, clinical examination, Doppler, and phlebographic examination. The data obtained lead them to propose this methodology as an important examination in the evaluation of upper thoracic pathology.     

Preliminary results of a multicentre trial of the electrically stimulated gracilis neoanal sphincter

BACKGROUND: The electrically stimulated gracilis neoanal sphincter was initially developed to treat refractory incontinence. Good early results were reported from the two centres that pioneered the technique. The aim of this study was to assess the operation in a prospective multicentre setting. METHODS: The procedure was performed on 64 patients from seven centres worldwide and was performed in stages. All patients were evaluated clinically and manometrically before and after operation. RESULTS: There was a high incidence of infective and hardware-related complications. At a median of 10 months following closure of the defunctioning stoma 56 per cent had experienced a good functional result. The major functional problems comprised evacuatory difficulties experienced by 25 per cent. CONCLUSION: The technique is effective in treating otherwise refractory incontinence. It is, however, a complex procedure and the morbidity rate may be high, particularly during the learning curve, factors that necessitate careful patient selection. Presented to the Association of Surgeons of Great Britain and Ireland in Bournemouth, UK, April 1997 and the European Council of Coloproctology in Edinburgh, UK, June 1997; and published in abstract form as Br J Surg 1997; 88(Suppl): 39 and Int J Colorectal Dis 1997; 12: 144     

Botulinum Toxin A for Oral Cavity Cancer Patients: In Microsurgical Patients BTX Injections in Major Salivary Glands Temporarily Reduce Salivary Production and the Risk of Local Complications Related to Saliva Stagnation

In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection) and to reconstruct the affected area by means of free flaps. The saliva stagnation in the post-operative period is a risk factor with regard to local complications. Minor complications related to saliva stagnation (such as tissue maceration and wound dehiscence) could become major complications compromising the surgery or the reconstructive outcome. In fact the formation of oro-cutaneous fistula may cause infection, failure of the free flap, or the patient’s death with carotid blow-out syndrome. Botulinum injections in the major salivary glands, four days before surgery, temporarily reduces salivation during the healing stage and thus could reduce the incidence of saliva-related complications. Forty three patients with oral cancer were treated with botulinum toxin A. The saliva quantitative measurement and the sialoscintigraphy were performed before and after infiltrations of botulinum toxin in the major salivary glands. In all cases there was a considerable, but temporary, reduction of salivary secretion. A lower rate of local complications was observed in the post-operative period. The salivary production returned to normal within two months, with minimal side effects and discomfort for the patients. The temporary inhibition of salivary secretion in the post-operative period could enable a reduction in saliva-related local complications, in the incidence of oro-cutaneous fistulas, and improve the outcome of the surgery as well as the quality of residual life in these patients.     

Presence of Hepatitis E Virus in a RED Deer (Cervus elaphus) Population in Central Italy

Hepatitis E is an acute human disease caused by the hepatitis E virus (HEV). In addition to humans, HEV has been detected in several animal species and is recognized as a zoonotic pathogen. Pigs, wild boar and deer can be reservoir. In this study, we evaluated HEV prevalence in a free‐living red deer (Cervus elaphus) population in central Italy by detecting virus‐specific antibodies and RNA in sera. A total of 35 of 251 red deer sera were positive for anti‐HEV IgG. HEV RNA was detected in 10 of 91 sera examined. Two genomic fragments targeted by diagnostic PCRs in the capsid region were sequenced, both matching with genotype 3 HEV. Overall results confirmed the occurrence of HEV infection in deer also in Italy.     

From the Cover: Emergence of dynamic vortex glasses in disordered polar active fluids

In equilibrium, disorder conspires with topological defects to redefine the ordered states of matter in systems as diverse as crystals, superconductors, and liquid crystals. Far from equilibrium, however, the consequences of quenched disorder on active condensed matter remain virtually uncharted. Here, we reveal a state of strongly disordered active matter with no counterparts in equilibrium: a dynamical vortex glass. Combining microfluidic experiments and theory, we show how colloidal flocks collectively cruise through disordered environments without relaxing the topological singularities of their flows. The resulting state is highly dynamical but the flow patterns, shaped by a finite density of frozen vortices, are stationary and exponentially degenerated. Quenched isotropic disorder acts as a random gauge field turning active liquids into dynamical vortex glasses. We argue that this robust mechanism should shape the collective dynamics of a broad class of disordered active matter, from synthetic active nematics to collections of living cells exploring heterogeneous media.

From a physicist’s perspective, flocks are ensembles of living or synthetic motile units collectively moving along a common emerging direction (1–4). They realize one of the most robust ordered states of matter observed over five orders of magnitude in scale and in systems as diverse as motility assays, self-propelled colloids, shaken grains, and actual flocks of birds (3, 5–10). The quiet flows of flocks are in stark contrast with the spatiotemporal chaos consistently reported and predicted in active nematic liquid crystals, another abundant form of ordered active matter realized in biological tissues, swimming cells, cellular extracts, and shaken rods (2, 11). Active nematics do not support any form of long-range order (4, 12). Their structure is continuously bent and destroyed by the proliferation and annihilation of singularities in their local orientation: topological defects (11, 13–15). Unlike in active nematics, topological defects in flocking matter are merely transient excitations which annihilate rapidly and allow uniaxial order to extend over system-spanning scales (4).This idyllic view of the ordered phases of active liquids is limited, however, to pure systems. Disorder is known to profoundly alter the stability of topological defects and the corresponding ordered states in equilibrium condensed matter (16–18), but its role in active fluids remains virtually uncharted territory. All previous studies (19–26), including our own early experiments (22), have been limited to weak disorder and smooth perturbations around topologically trivial states. Unlike in equilibrium, no available experiment, simulation, or theory has ever demonstrated or predicted disorder-induced topological excitations in active matter.In this paper we show how isotropic disorder generically challenges the extreme robustness of flocking matter to topological defects. We map the full phase behavior of colloidal flocks navigating through disordered lattice of obstacles and reveal an unanticipated state of active matter: a dynamical vortex glass. In dynamical vortex glasses, millions of self-propelled particles can steadily cruise through disorder, maintaining local orientational order and without relaxing the topological singularities of their flows. The associated flow patterns are exponentially degenerated and shaped by amorphous ensembles of frozen topological defects, yielding a dynamical state akin to the static vortex-glass phase of dirty superconductors and random-gauge magnets (27–29). Building a theory of flock hydrodynamics beyond the spin-wave approximation, we elucidate the emergence and stabilization of topological vortices by quenched disorder. Finally, we discuss the universality of the dynamical vortex glass phase beyond the specifics of polar active matter and colloidal flocks.     

Virologic and genetic evaluation of vemurafenib-induced skin cancers

We describe the occurrence of a giant squamous cell carcinoma in a patient receiving vemurafenib for the treatment of late melanoma mestastases. Although the development of keratoacanthomas and squamous cell carcinomas (SCC) has been described during vemurafenib therapy, most of the reported cases are treated with surgical excision. In the present case, SCC regressed after drug withdrawal.     

The Role of Rehabilitation in Patients With Progressive Supranuclear Palsy: A Narrative Review

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder caused by the deposition of abnormal proteins in neurons of the basal ganglia that limit motor ability, resulting in disability and reduced quality of life. So far, no pharmacologic therapy has been developed, and the treatment remains symptomatic. The aim of the present study is to perform a systematic investigation of the literature, and to determine the types and effects of rehabilitative interventions used for PSP. A search of all studies was conducted in MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, CINAHL, and EMBASE. Twelve studies were identified, including 6 case reports, 3 case series, one case-control study, one quasi?randomized trial (i.e. not truly random) with crossover design, and one randomized controlled trial, with 88 patients investigated overall. Rehabilitative interventions varied in type, number, frequency, and duration of sessions. The most commonly used clinical measures were the Progressive Supranuclear Palsy Rating Scale (PSPRS) and Unified Parkinson's Disease Rating Scale (UPDRS). Physical exercises were the main rehabilitative strategy but were associated with other interventions and rehabilitative devices, in particular treadmill and robot-assisted gait training. All studies showed an improvement in balance and gait impairment with a reduction of falls after rehabilitation treatment. Because of poor methodological quality and the variety of rehabilitative approaches including different and variable strategies, there was insufficient evidence of the effectiveness of any specific rehabilitation intervention in PSP. Despite this finding, rehabilitation might improve balance and gait, thereby reducing falls in PSP patients.

A contribution to the morphology of tortuosity of arteries, aneurysms and arteriomegaly.

Using the electron microscope, the authors examined the structure of the wall in a case of arteriomegaly of the inferior mesenteric artery in man. Structural changes concerned the elastic material showing signs of degeneration. Based on a comparison with literary findings, the authors conclude that tortuosity of the arteries, aneurysms and arteriomegaly are caused by congenital, age-dependent and pathological changes in the elastic material in the vessel wall. There exist basic structural differences in the arterial wall in arteriomegaly and in atherosclerosis.     

Pathology of the defunctioned rectum in ulcerative colitis.

Faecal stream diversion may induce inflammatory changes in the defunctioned segment of the large intestine. These changes are predominantly mucosal, although confusing histological features including granulomas may be present. The pathology of 15 defunctioned rectal stumps has been studied. All patients had previously undergone urgent total colectomy for ulcerative colitis and rectal stumps had been left in situ while they awaited pelvic ileal reservoir construction. All rectal stumps showed predominantly mucosal disease but there were additional features such as florid lymphoid follicular hyperplasia (12 cases), transmural inflammation (nine cases), granulomas (four cases), fissures (eight cases), and changes akin to ischaemia or to pseudomembraneous colitis (four cases). These changes may result from a combination of defunctioning and of active ulcerative proctitis. Some induce a histological appearance that may mimic Crohn's disease. Nevertheless review of all 15 colectomy specimens showed unequivocal ulcerative colitis and none of the patients has subsequently shown any clinical, radiological, or pathological evidence to support a diagnosis of Crohn's disease. Histology of the rectal stump in ulcerative colitis may lead to an erroneous diagnosis of Crohn's disease and the patient may subsequently be denied the advantage of a pelvic ileal reservoir.