Site of metastatic recurrence impacts prognosis in patients with high-grade upper tract urothelial carcinoma

PurposeMetastatic recurrence occurs in over 25% of upper tract urothelial carcinoma patients treated with radical nephroureterectomy. While metastatic recurrence suggests poor prognosis, the impact of the specific site of recurrence on prognosis is not well documented.Materials and methodsWe retrospectively analyzed 188 patients who underwent radical nephroureterectomy for high-grade, node-negative upper tract urothelial carcinoma at our institution from 2003 to 2018 without receiving neoadjuvant or adjuvant chemotherapy. Competing-risks survival analysis was performed to evaluate the cumulative incidence and predictors of metastatic recurrence. The Kaplan-Meier method and log-rank test were used to estimate and compare recurrence site-specific survival probabilities following metastatic recurrence. Cox regression analyses were performed to assess site-specific prognoses.ResultsOf the 188 patients, 47 (25%) developed metastatic recurrence over a median follow-up of 30 months (interquartile range: 10.5–58.5 months). The 1- and 2-year cumulative incidences of metastatic recurrence were 13.6% and 23.6%, respectively. On multivariable analysis, lymphovascular invasion was significantly predictive of metastatic recurrence (subhazard ratio: 2.6, P = 0.01). Of the 47 patients who developed recurrence, 38 (80.9%) died over a median follow-up of 10 months (interquartile range: 5–20 months). Metastatic recurrence was most common in the lungs (n= 13, 28%) and at multiple sites (n= 14, 30%). Median time to recurrence was shorter for recurrences at multiple sites (6.5 months) and those in the liver (13 months) and bone (18 months) compared to other sites. Patients who recurred in the liver (hazard ratio: 6.3, P = 0.007), bone (hazard ratio: 4.9, P = 0.02), and multiple sites (hazard ratio: 4.6, P = 0.01) had significantly worse prognosis compared to those who recurred in lymph nodes. Statistical significance persisted after adjusting for treatment with salvage therapy.ConclusionsA significant proportion of high-grade upper tract urothelial carcinoma patients recur systemically after radical nephroureterectomy. Lymphovascular invasion is a predictor of metastatic recurrence and may inform decisions regarding perioperative chemotherapy. Hepatic and osseous recurrences have relatively quicker onset and less favorable prognosis compared to other sites. These findings may benefit future efforts to develop recurrence site-specific treatment plans and highlight the necessity of subsequent endeavors to explore the genetic associations of recurrence in upper tract urothelial carcinoma.     

Health care delivery system. Effects on surgical education: The Mexican panorama

Health care delivery in Mexico is divided in three groups: a social sector that covers approximately 53% of the population and is financed by the labor force, the state and the employer; a public, or open, sector that covers 33% of the population and is financed by federal and state funds; and a private sector that covers about 5% of the population and has two categories, the not-for-profit hospitals and the profit-oriented institutions. Most medical practitioners can work in any of the three groups or in several. Nine percent of Mexico's population, because of extreme ignorance, poverty, or isolation, have no or limited access to medical care. Mexico has 58 medical schools, which graduate about 7800 new physicians annually, awarding them the title Medico cirujano (Physician Surgeon). There are more than 160,000 physicians in Mexico, 20,000 of whom are unemployed. Each year, approximately 12,000 physicians compete for the 4306 places in the official residency training programs for all specialties. Of those taking the examination, 2000 try to get one of the 625 slots available for training in general surgery. Most of the surgical training programs in Mexico have a 3-year duration. The Mexican Academy of Surgery, the Mexican Society of General Surgery, and the Mexican Board of Surgery, as well as private individuals and organizations, are working to improve the quality of medical education and trying to establish a 5-year training program in surgery. The rapid movement toward modernization that is sweeping the country must include the improvement of surgical education as well.

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Resumen La atención de la salud en México está dividida en tres grupos: el Sector Social que cubre approximadamente el 53% de la población y que está financiado por la fuerza laboral, el Estado y el empleador; un Sector Público o Abierto que cubre el 33% de la población y que es financiado con fondos federales y estatales; y un Sector Privado que cubre el 5% de la población y que posee dos categorías: la de los hospitales sin ánimo de lucro y la de las instituciones con ánimo de lucro. La mayoría de los médicos pueden trabajar en cualquiera de los 3 grupos, o en combinación. El 9% de la población mexicana, por extrema ignorancia, pobreza y aislamiento no posee acceso alguno, o sólo lo tiene mínimo, a la atención médica.México posee 58 facultades de medicina, las cuales gradúan alrededor de 7.800 nuevos médicos anualmente, a quienes se les expide el título de médico cirujano.Hay más de 160.000 médicos en México, 20.000 de los cuales se encuentran desempleados. Cada año aproximadamente 12.000 médicos compiten por las 4.306 plazas en los programas oficiales de adiestramiento en las diferentes especialidades. De aquellos que presentan examen, 2.000 tratan de obtener uno de los 625 lugares disponibles para adiestramiento en círugía general.La mayoría de los programas de adiestramiento quirúrgico en la nación son de tres años de duración. La Academia Mexicana de Cirugía, la Asociación Mexicana de Cirugía General y el Consejo Mexicano de Cirugía, así como individuos y organizaciones privadas, trabajan en pro del mejoramiento de la calidad de la educación médica y tratan de establecer un programa de adiestramiento en cirugía de cinco años de duración. Los rápidos cambios de modernización que ocurren en el país deben incluir también el mejoramiento de la educación quirúrgica.

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Résumé L'administration des soins au Mexique est repartie entre trois secteurs: 1) Le secteur social qui couvre environ 53% de la population et qui est financé par la caisse des ouvriers, celle de l'état et celle du patronat; 2) un secteur public ou ouvert, qui couvre environ 33% de la population et qui est financé par des fonds fédéraux et gouvernementaux et enfin 3) un secteur privé, qui ne couvre que 5% environ de la population et qui comprend deux catégories, les hôpitaux à but non-lucratif et les institutions à but lucratif. La plupart des médecins peuvent exercer dans un ou plusieurs de ces trois groupes. Neuf pourcent de la population, en raison d'une extrême pauvreté, de son ignorance ou de son éloignement, a peu ou pas d'accés à des soins structurés.Il y a 58 écoles de Médecine au Mexique, produisant environ 7800 nouveaux médecins par an. Ils reçoivent le titre de Medico Cirujano littéralement, Médecin chirurgical. Il existe plus de 160000 médecins au Mexique, dont 20000 sont sans travail. Chaque année, environ 12000 médecins sont en compétition pour obtenir un des 4306 postes officiels de résidents, toutes spialités confondues. Parmi ceux qui se présentent, 2000 sont candidats pour un poste en chirurgie. La plupart des programmes d'enseignement durent trois ans. L'Académie de Chirurgie Mexicaine, La Société Mexicaine de chirurgie Générale et le comité d'accréditation chirurgicale, tout en accord avec les institutions privées et leur dirigeants oeuvrent pour un programme de cinq ans. La vague de progrès, ressentie dans tous les domaines, qui traverse actuellement le pays doit aussi intéresser l'amélioration de l'enseignement en chirurgie.

     

P53 alterations show significant correlation with gene amplification and s-phase index in breast-cancer

Correlation of p53 gene/protein alterations with incidence of oncogene amplification, a potential marker of prognosis, was evaluated in 26 fresh breast cancer samples. p53 gene was analyzed by SSCP and DNA sequencing while p53 protein status was investigated by immunohistochemistry (IH). Amplification of c-erbB2/neu, c-myc, N-ras, int-2, hst, PRAD-1 and EGFR genes was studied by slot blot and in situ hybridizations. p53 alterations were found in 31% cases by SSCP and 42% by IH; gene amplification was detected in 27% cases. p53 gene alterations correlated significantly with gene amplification (p=0.006) and also with higher S-phase index (p=0.026), aneuploidy (p=0.026) and negative progesterone receptor status (p=0.043).     

Tumoral calcinosis in infancy

The most frequent form of idiopathic calcinosis is tumoral calcinosis (TC) which rarely occurs at young ages. We describe here a TC case of a young boy with its light microscopy completed with electron microscopic examinations. X-ray microanalysis revealed in the intracellular crystals CaCl₂ besides the previously described hydroxyapatite. The significance of this finding is unknown at the moment.     

A preliminary examination of cryotherapy and secondary injury in skeletal muscle

PURPOSE: The purpose of this study was to document the presence of secondary injury in skeletal muscle, to quantify it, and to determine whether it is altered by acute cryotherapy. METHODS: Crush injuries to the triceps surae of 19 adult male Sprague-Dawley rats were either treated continuously with ice for 5 h (N = 10) or received no ice treatment (N = 9). After treatment, tissues were assayed for the reduction of triphenyltetrazolium chloride (TTC) to triphenylformazan (formazan red). TTC reduction is indicative of oxidative function and serves as an indicator of cellular damage. RESULTS: A significantly lower TTC reduction rate was seen in both cold-treated injured tissue (6.59 +/- 1.01 microg x mg(-1) x h(-1)) and nontreated injured tissue (4.48 +/- 0.79 microg x mg(-1) x h(-1)) compared with uninjured controls (ice group = 7.94 +/- 1.49 microg x mg(-1) x h(-1), no-ice group = 6.62 +/- 0.75 microg x mg(-1) x h(-1)). These data indicate that crushing of muscle tissue produces injury measurable with the TTC reduction assay. Additionally, in crush-injured tissues, a significantly lower TTC reduction rate was seen in untreated tissues (4.48 +/- 0.79 microg x mg(-1) x h(-1)) compared with ice treated tissues (6.59 +/- 1.01 microg x mg(-1) x h(-1)), indicating that cryotherapy reduces the magnitude of secondary injury. CONCLUSIONS: From these data, it can be concluded that secondary injury occurs after primary crush injury and that secondary injury is retarded by acute treatment with 5 h of continuous cryotherapy.     

Supine Bicycle Exercise Echocardiography: A Potent Immediately Available Tool for Detection and Localization of Myocardial Ischemia for the Initial Cardiologist

Background: Exercise echocardiography (EE) is being used increasingly as an investigative technique now that dynamic images can be captured digitally. Its equivalent reliability with scintigraphic methods has been demonstrated in a hospital setting. This study analyzes its impact on daily practice. Materials and Methods: Standardized progressive stress was produced by supine bicycle ergometry. Echocardiographic images of complete cardiac cycles were obtained in standard apical and parasternal short-axis views before, during, and after maximum effort, and digitized for simultaneous analysis of synchronized images at rest and during exercise. Two hundred sixteen patients (175 men and 41 women; mean age 58 ± 10 years) were studied. Results: Image quality was suboptimal in 4 cases. In the remaining 212 cases, ischemia was detected in 91 cases, and the test was negative in 114 cases and doubtful in 7 cases. Control by selective coronary angiography, as indicated by the clinical situation, was performed in 52 cases. In this particular group, EE showed 87% sensitivity, which is significantly higher than the 59% recorded for conventional exercise testing (P > 0.0001). Conclusions: EE by bicycle ergometer in the supine position is a valid, noninvasive investigative technique that can be used in an outpatient situation (feasibility 95%) since it is readily available. Its value appears to be greatest in cases in which exercise ECG is not conclusive. A negative result enables the initial cardiologist to reassure the patient immediately, which has been demonstrated in the literature to have favorable prognostic value.     

The differential effects of haloperidol and methamphetamine on time estimation in the rat

Forty rats were trained to make a left lever response if a signal (white noise) was 2.5s and to make a right lever response if the signal was 6.3s. When seven intermediate signal durations, to which responses were not reinforced, were randomly interspersed the probability of a right-lever (long) response increased as a function of signal duration. Methamphetamine shifted this psychometric function leftward and decreased its slope: haloperidol also decreased the slope but shifted the function rightward. A combination of haloperidol and methamphetamine led to a function similar to the saline control function. The leftward shift probably reflects an increase in the speed of an internal clock, and the rightward shift probably reflects a decrease in its speed. Since methamphetamine releases several catecholamines, including dopamine, and haloperidol blocks dopamine receptors, it is plausible that the horizontal location of the psychometric function (the speed of the clock) is related to the effective level of dopamine.     

Organization of nucleoli and nuclear bodies in osmotically stimulated supraoptic neurons of the rat

This study has analyzed variations in the number of nucleoli and nuclear bodies, as well as in their ultrastructural and cytochemical organization, after the osmotically induced activation of supraoptic nucleus (SON) neurons of the rat. The number of nucleoli and nuclear bodies and also the nucleolar size were determined on smear preparations of previously block-impregnated SON. The mean number of nucleoli per cell was 1.35 +/- 0.6 (mean +/- SDM) in control rats. No significant variations in this value were registered either in dehydrated or rehydrated rats. The mean nucleolar volume and the total nucleolar volume per cell showed a significant increase in dehydrated rats with respect to the controls, whereas these two parameters tended to return to control values in rats rehydrated after dehydration. The mean number of nuclear bodies per cell increased significantly from 0.56 +/- 0.50 (mean +/- SDM) in control rats to 1.54 +/- 1.1 after 6 days of dehydration. By electron microscopy, SON neurons displayed a reticulated nucleolar configuration. After the osmotically induced neuronal activation, there was an increase in the proportion of the total nucleolar area occupied by the granular component, and also a reduction in the mean fibrillar-center area. The most characteristic nucleolar features in rehydrated rats were the tendency for the granular component to be segregated and the occurrence of intranucleolar vacuoles. Ultrastructural cytochemistry with a specific silver method revealed a selective silver reaction on the coiled threads of the nuclear bodies--identified as "coiled bodies"--and on the nucleolar fibrillar components in all animal groups studied. Since nucleoli play a major role in ribosome biogenesis, a relationship between these nucleolar changes and the level of cellular activity of SON neurons is proposed. Furthermore, the response of nuclear "coiled bodies" to neuronal activation suggests their participation in the processing and transport of rRNA precursors.     

Angiographic Embolization for Intraperitoneal and Retroperitoneal Injuries

Angiographic embolization (AE) has been used extensively for bleeding control after injuries to the face and neck. Its role in abdominal trauma requires further exploration. We reviewed the medical records of 137 consecutive patients who underwent angiography with the intent to embolize bleeding sites within the abdomen. Of them, 97 (71%) had blunt and 40 (29%) had penetrating trauma. AE was performed for hemorrhage associated with pelvic fractures (97 patients), liver lacerations (n= 26), renal lacerations (n= 12), splenic lacerations (n= 5), other injuries (n= 9), and multiple injuries (n= 12). On angiography, 102 patients were found to have bleeding sites and underwent AE, with angiographic and clinical bleeding control in 93 (91%). The rate of successful hemostasis by AE was identical in blunt and penetrating trauma patients. There was no major morbidity after AE. No factors predicted patients with a high likelihood to have a positive angiogram. Patients who had AE before or after a period of attempted hemodynamic stabilization in the intensive care unit were no different with respect to hemodynamic parameters immediately before AE or effectiveness of AE for bleeding control. AE is a safe and effective method for controlling bleeding after blunt and penetrating intra- and retroperitoneal injuries. Early AE may be used in selected patients as a front-line therapeutic intervention that offers expeditious hemostasis and prevents delays in definitive bleeding control.