Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

[The concept of hypervitaminosis as a dysvitaminosis and its relationship with overdosage and overload. Etiopathogenetic classification of dysvitaminoses]. / Il concetto di ipervitaminosi come una disvitaminosi e rapporti con iperdosaggio e sovraccarico. Classificazione etiopatogenetica delle disvitaminosi.

The incorrect use of the terms vitamin overdosage and overload, hypervitaminosis and dysvitaminosis gives rise to errors in the classification and evaluation of their etiology and pathogenesis. Vitamin overdosage and overload are observed with every vitamin and produce high blood and tissue levels of the vitamin itself; however, the overdosage can be obtained only upon administration of high doses of a vitamin, while vitamin overload may originate from a variety of factors. Hypervitaminoses are known for vitamin A and D; they are accompanied by high blood levels, but are characterized by a specific symptomatology. The term dysvitaminosis comprises "every alteration of the physiological status of the vitamin, in terms of both its deficiency and its surplus". These considerations provide a unitary view of vitamin pathology and lead to the following proposal of an etiopathogenetic classification of dysvitaminoses: class A) dysvitaminoses due to overload, class B) dysvitaminoses due to deficiency. Each class in turn may be divided into congenital and acquired syndromes. In class A) the congenital syndromes are still not well known, the acquired syndromes comprise those with hypervitaminosis (hypervitaminosis A and D) and those without hypervitaminosis (for the other vitamins). In class B) the congenital syndromes comprise diseases produced by inborn enzymatic errors and by other etiologies, the acquired syndromes can be distinguished in physiological (age, pregnancy, etc.) and pathological (nutritional, iatrogenic, etc.) ones. On this basis hypervitaminoses A and D can be considered as non obligatory dysvitaminoses due to overload; their origin has a complex etiology, since the liposolubility of the vitamins and the prolonged use of high dosages are not the only factors responsible for the hypervitaminosis.

[Drug-induced avitaminoses and their prevention (author's transl)]. / Avitaminoses da farmaci e loro prevenzione.

The concept of "drug induced avitaminoses" originates from the observation that drugs may cause vitamin deficiencies. These avitaminoses belong to the "iatrogenic disvitaminoses" and can be subdivided into two groups since they may either represent unwanted side effects of a drug or may be utilized for therapeutical purpose. In the latter case they can be considered as "planned avitaminoses". All drugs are generally able to produce a deficiency of one or more vitamins and therefore have a "devitaminizing power". It would be desirable to quantify this property of drugs in terms of a "devitaminization index". Knowledge of this index, which should be acquired for new drugs during clinical research, is of primary importance since it allows to adapt the dosage and use of the drug to the vitaminic status of the patient and enables to foresee and prevent damages due to vitamin deficiency. Drug induced avitaminioses are produced more easily and are more severe if the devitaminizing power of the drug and its dosage are high, the therapy is long and the vitaminic status of the patient is optimal. Many subjects (old people, children, etc.) have an elevated risk of avitaminoses. Drug induced avitaminoses are produced by mechanisms acting both at the intestinal level (absorption, endogenous production, etc.) and at the tissue level (metabolism, utilization, etc.). Some of the mechanisms have not been completely clarified. These avitaminoses are numerous and frequent, but their prevention is relatively easy and always achievable. They constitute a new disease and cause an additional damage with respect to the primary illness. The social and economic aspects of this damage are evident considering that many pharmacological profilactic and therapeutic treatments of social illnesses, such as diabetes, tuberculosis, epilepsy, rheumatic diseases, etc. have a devitaminizing power. It is clear therefore that this pathology is particularly important in preventive medicine and that it must be known not only by practitioners and biologists but also outside the medical field.

[Vitaminology for practitioners. II. Avitaminoses, risk, latency period, classification]. / Aggiornamenti di vitaminologia per il medico. Parte II. - Avitaminosi: rischio, latenza, classificazioni.

The concept of risk in the field of avitaminoses is very important and useful for the practitioner, who should consider two aspects: a) risk factors, which could be individual (physiological, pathological and psychological) and extra-individual (alimentary, environmental, etc.); b) subjects with an elevated risk of avitaminosis (childhood, old age, pregnancy, etc.). In these subjects the risk can be a generical one, when there is an elevated requirement for all vitamins (nursing women, sportmen, etc.) or a specific one, when there is a high requirement only for a single vitamin (osteomalacia, some professional diseases, use of oral contraceptives) or a vew of them (alcoholism, diabetes, etc.). On the basis of this kind of knowledge it is easy for the practitioner to estimate which vitamins are necessary for each subject or for a group of subjects in physiological or in pathological conditions. For example, there is an elevated risk of apyridoxinosis in old age (acalciferolosis in aged women), of athiaminosis and apyridoxinosis in diabetes, of apyridoxinosis in oral contraceptives users, of axeroftolosis in hyperthyroidism, of athiaminosis, apyridoxinosis, aniacinosis and anascorbosis in alcoholics. In the second chapter the concept of the latency period in avitaminosis is illustrated. This period corresponds to the interval between the moment when deficiency stimulus starts operating and the moment when its effect, that is the picture of avitaminosis, appears. The latency time is not measurable, on account of the difficulties in establishing the onset of the deficiency stimulus; generally it is very long and is followed by the period of biochemical symptomatology and subsequently by the one of clinical symptomatology. Each of these three phases can be further divided in several steps, which have summarized in a Table. The last chapter is dedicated to the classification of avitaminoses. From the etiopathogenetic point of view avitaminoses can be due to: a) deficiency of introduction (alimentary level)); b) deficiency of absorption (enteric level); c) deficiency of utilization (tissue level). From the clinical point of view avitaminoses can be distinguished in deficiency with: a) a complete clinical symptomatology (scurvy, beriberi, pellagra, rickets, osteomalacia, xerophthalmia, hemeralopia); b) an incomplete clinical symptomatology (mono- or oligo-symptomatic or partial clinical picture); c) a biochemical symptomatology only (subclinic or clinically asymptomatic picture).

[Changes in opposite directions of tryptophanpyrrolase and 3-OH-anthranilic oxidase after a loading dose of tryptophan]. / Variazioni in senso opposto della triptofano pirrolasi e della 3-OH-antranilico ossidasi dopo un carico di triptofano.

A loading dose of tryptophan induces a marked increase of tryptophan-pyrrolase (substrate induction) and a decrease of 3-OH-anthranilic-oxidase values in rat liver; in the kidneys of the same experimental animals the 3-OH-anthranilic-oxydase is instead unchanged. In other experimental conditions (surrenectomized or pyridoxine depleted rats, with or without tryptophan loading; with prednisolone loading) a more or less important substrate induction is always reported, whereas no variation occurs in the values of 3-OH-anthranilic-oxydase. These data are not sufficient to state whether there is a connection between the opposite responses of the two enzymatic activities obtained after tryptophan loading in rat liver homogenate. On the other hand, it should be kept in mind that they do not represent the overall effect induced by the aminoacid loading, but refer only to one moment of the action exerted by the loading itself. In order to acquire a thorough knowledge of the observations made so far and to formulate some assumptions which may be helpful for the interpretation of the relevant mechanisms, it is necessary to investigate the kinetics of both enzymes, and to study their regulatory mechanisms in particular after tryptophan loading.

[Vitamin B1 and autonomic drugs: a reprint]. / Vitamina B1 e farmaci del sistema nervoso vegetativo: una ristampa.

The problem of the relationship between the thiamine and autonomic system drugs was studied about 30 years ago. To the vitamin was attributed an excitatory effect upon the peripheric section of parasympathetic nervous system and a synergic action with acetylcholine. Both an acetylcholine-like substance and thiamine are liberated at the nerve terminals after a stimulation. A similar synergic action of thiamine with adrenaline was also demonstrated. The study of the relationship between these drugs and the vitamin B1 is also now interesting. We want to stimulate a new series of experiments on this subject with the reprint of this review.