Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma.

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.

Iliac artery-ureteral fistula: a fatal hemorrhage in a man with ureterocutaneostomy.

Primary and secondary artery-ureteral fistulas are a rare condition. In this case report we describe a case of misunderstood iliac artery-ureteral fistula, with negative radiological preoperative imaging, which occurred in a man as late complication of ureterocutaneostomy.

[Neuroendocrine bladder cancer: oncological emergency?].

Neuroendocrine bladder cancer is extremely rare, with an estimated incidence of 0.5%- 0.7%. In bladder cancers there is no evident connection between the neuroendocrine phenotypic expression and the clinical history. However, prognosis is usually poor and the survival rate at 5 years does not exceed 8%, if untreated. METHODS. We are here describing three case reports of bladder carcinoma with neuroendocrine differentiation, which is extremely aggressive and leads rapidly to death. At the present time, the local control of these tumors is achieved by radical cystectomy and radiotherapy; they can be both associated to chemotherapy. However, since these lesions are fairly rare, there is no gold standard therapy and there are no prospective studies on the management of these tumors. CONCLUSIONS. Considering the quick evolution and progression of any variant of the neuroendocrine tumors of the bladder, urologists and anesthetists should see them as real oncological emergencies. A prompt intervention through radical surgery with cystectomy and linfadenectomia, and the anathomo-pathologist's systematic investigation of the scraps could make the approach therapeutic and not only palliative. Prospective studies on neo-adjuvant chemotherapy as well as experimental studies about target therapies may yield new guidelines on the tumor management.

Is gastric ulceration different in normal and malnourished rats?

Protein malnutrition can adversely affect all tissues. The aim of the present study was to test the hypothesis that protein deprivation influences gastric ulcer formation, as well as metabolism and organ growth, in rats. In the present study, there was a significant reduction in the body and organ weight of rats fed a low-protein diet (P<0.001). Malnourished rats were less susceptible to ulceration of the gastric mucosa in ethanol and indomethacin models of acute gastric ulcers when compared with rats fed a normoproteic diet (17 % protein). Mucus production and prostaglandin E2 formation increased in malnourished rats, possibly explaining the lower number of acute ulcers in these animals. Pylorus ligature altered gastric juice composition (increased pH and gastric volume, and decreased total acid concentration) in the animal group fed a low-protein diet compared with the group fed a diet containing 17 % protein (P<0.05). The gastric mucosa was more damaged in malnourished rats than in normal rats evaluated for 14 d after acetic acid injection (P<0.001). Malnourished rats exhibited resistance to acute gastric lesions, owing to an increase in prostaglandin GE2 release and mucus secretion, which protected their gastric mucosa. This phenomenon was not seen in subchronic gastric ulceration.

Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.

The use of tetrahydropyrimidinones as an alternate scaffold for designing HIVPR inhibitors has advantages, over the previously disclosed hexahydro-1,3-diazepin-2-ones, of being more unsymmetrical (different P1/P1'), less crystalline, more soluble, and more lipophilic (mono-ol vs diol). They show a better translation of Ki to IC90 for the more polar P2 groups that in general give the more potent enzyme inhibitors. Structure-activity relationship (SAR) studies of the tetrahydropyrimidinones showed that the phenylethyl P1' substituent, the hydroxyl group, and the urea carbonyl are all critical for good activity. However, there was significant flexibility in the possible P2/P2' substituents that could be used. Many analogues that contained identical or different P2/P2' substituents, or only one P2 substituent, were found to have excellent enzyme potency and several had excellent antiviral potency. Several of these compounds were examined for oral bioavailability in the rat or the dog at 10 mg/kg. However, the oral bioavailability of the tetrahydropyrimidinones was, in general, less than the corresponding hexahydro-1,3-diazepin-2-ones. Unfortunately, when all factors are considered, including potency, protein binding, solubility, bioavailability, and resistance profile, the tetrahydropyrimidinones did not offer any advantage over the previously disclosed hexahydro-1,3-diazepin-2-ones series.

[Reflex epilepsy: study of 5 cases]. / Epilepsias reflexas: estudo de 5 casos.

Five clinical cases of reflex epilepsy with the EEG records during the seizure are provided. A review of the clinical aspects and EEG characteristics of these epilepsies is made. Its physiopathology is discussed and the findings compared to those in the literature.

[Polyneuropathy in the course of hyperthyroidism: report of a case]. / Polineuropatia no curso do hipertireoidismo: relato de um caso.

The authors report a pertinent documented with subsidiary examination uncommon case of sensitive-motor polyneuropathy, in the course of hyperthyroidism, looking like be coherent to give it the name of "thyrotoxic polyneuropathy". In despite of few scientific works on this subject, strong arguments are presented intending to link the process of hyperthyroidism and the progressive degeneration, distal, symmetric and simultaneous, of peripheric nerves. Final considerations show the difficulty of recognizing the etiopathogeny of the degenerative process of peripheral nerves remembering the possibility of toxic, carencial or auto-immune nature.

Polineuropatia no curso do hipertireoidismo. Relato de um caso. / Polyneuropathy in the course of hyperthyroidism. Report of a case

Os autores apresentam, com apropriada documentacao de exames subsidiarios, a discussao de caso inusitado de polineuropatia sensitivo-motora, no curso de franco processo hipertireoidiano,parecendo mesmo ser coerente denomina-lo de "polineuropatia tireotoxica". A despeito do escasso numero de trabalhos a proposito do tema, fortes argumentos sao lembrados no sentido de se ligar o processo hipertiroidismo a progressiva degeneracao simultanea, simetrica e distal dos nervos perifericos. Ao final, mostra-se a dificuldade de se reconhecer a etiopatogenia do processo de degeneracao dos nervos perifericos, lembrando, porem, a possibilidade de ser de natureza toxica, carencial ou auto-imune

Epilepsias reflexas: estudo de 5 casos. / Reflex epilepsies: study of 5 cases

Relato de 5 casos de epilepsias reflexas tracados eletrencefalograficos ictais. As diversas formas clinicas e eletrencefalograficas encontradas nesses grupos de epilepsias sao expostas. A fisiopatologia e analisada comparando os achados com os colhidos na literatura

[Computerized tomography of the skull in the diagnosis of meningiomas. Report of 16 cases]. / Tomografia computadorizada do crânio no diagnóstico dos meningiomas.

The authors report the usefulness of the skull's computerized tomography for the exact diagnosis of the meningiomas. The 16 cases reported were comproved surgical and histologically. The average was 52.1 years. They dealt out 10 females and 6 males. According to their localization, there are 5 on the orbital cavity and/or sphenoid ridge (31.2%), 3 of the falx (18.7%), 3 parasagitals (18.7%), 2 suprasellars (12.5%), 2 of the convexity (12.5%) and 1 of the tentorium (6.2%). The authors concluded that the computerized tomography of the skull is of high positiveness (95-98%), without damages for the patient, and nowadays it allows precocity in diagnosis, and, consequently, with better therapeutic results.

Tomografia computadorizada do cranio no diagnostico dos meningiomas:registro de 16 casos. / Computerized tomography of the skull in the diagnosis of meningiomas. Report of 16 cases

Os autores se referem a importancia do emprego da tomografia computadorizada do cranio para o preciso diagnostico dos meningiomas. Constam da experiencia 16 casos comprovados cirurgica e histologicamente. A media de idade foi de 52,1 anos, sendo 10 pacientes do sexo feminino e 6 masculino. Quando a localizacao, 5 eram da cavidade orbitraria e/ou asa do esfenoide, 3 parasagitais, 3 da foice, 2 supra-selares, 2 de convexidade e 1 do tentorio. Concluem tratar-se de exame de grande positividade (95-98%), praticamente inocuo e que permite, na atualidade o diagnostico precoce conduzindo, consequentemente, a melhores resultados terapeuticos.