[Sentinel lymph node dissection for localized prostate cancer]. / Papel de la biopsia dinámica del ganglio centinela en el cáncer de próstata organoconfinado.

Proper assessment of lymph node status is of crucial importance in the management of newly diagnosed prostate cancer. Early stage metastatic disease takes the form of microscopic tumor-cell deposits rather than grossly enlarged nodes. So far there is no imaging technique, however, which allows detecting small metastases in the range of a few millimetres. Therefore pelvic lymph node dissection (PLND) is the only reliable method of staging for clinically localized prostate cancer. The cornerstone of radioguided prostate surgery is a radiopharmaceutical--a carrier molecule labeled by radionuclide. After injection to at the prostate, the radiopharmaceutical crosses the lymphatic pores and migrates into the lymph vessels and from there to the first echelon of lymph nodes. We were the first to show that sentinel PLND can be performed by means of laparoscopy preceding laparoscopic radical prostatectomy. Our most recent publication presents data of 140 patients with clinically localized prostate cancer in which laparoscopic sentinel PLND was performed preceding radical prostatectomy from November 2001 to January 2005. On the preoperative scintigraphy SLNs were detected bilaterally,unilaterally, not on the pelvic-walls in 113 (80.7%), 20 (14.2%) and 6 (4.2%) patients and intraoperatively in 96 (68.6%), 36 (25.7%), 8 (5.7%) patients respectively. In 99 out of 140 patients (70.7%) intraoperatively SLN was detected in the same position as on preoperative scan. At least one SLN was detected in 133 patients (95.3%). Whenever PLND is indicated it should not be limited to lymph node sampling as provided by standard limited PLND but has to be performed in the template of extended PLND. There is only limited experience with sentinel PLND, but all the data collected so far indicate that this method has the potential to become an alternative to extended PLND since it allows for reduction of the extent of PLND without compromising diagnostic accuracy.

Papel de la biopsia dinámica del ganglio centinela en el cáncer de próstata organoconfinado / Sentinel lymph node dissection for localized prostate cancer

La correcta valoración de la afectación ganglionar es de gran importancia en el manejo de los nuevos casos de cáncer de próstata. El estadio precoz de la enfermedad metastásica se manifiesta como pequeños focos microscópicos más que como ganglios linfáticos engrosados. Sin embargo, hasta ahora no hay ninguna técnica de imagen que permita detectar metástasis cuyo diámetro alcance unos pocos milímetros. Por tanto, la linfadenectomía pélvica (LNDP) es el único método fiable para el estadiaje del cáncer de próstata organoconfinado (CPO). El pilar de la cirugía prostática radioguiada es el uso de un radiofármaco, una molécula transportadora marcada con radionúclido. Tras la inyección en la glándula prostática, el radiofármaco alcanza el territorio linfático y migra al primer escalón linfático, el ganglio centinela (GC). Fuimos los primeros en demostrar que la LDNP del GC se podía llevar a cabo mediante abordaje laparoscópico previo a la prostatectomía radical (PTR) laparoscópica. En nuestra publicación más reciente se presentan los datos de 140 pacientes diagnosticados de CPO entre noviembre de 2001 a enero 2005 en los que se realizó LDNP laparoscópica del GC previa a la PTR, también laparoscópica14. En la gammagrafía preoperatoria, se detectaron GC de forma bilateral en 113 pacientes (80,7%), de forma unilateral en 20 (14,2%) y no se detectaron en 6 (4,2%), mientras que en la realizada durante la cirugía se detectaron en 96 pacientes (68,6%), 36 (25,7%), 8 (5,7%) respectivamente. Los GC se hallaron en la misma localización con ambos procedimientos en 99 de 140 pacientes (70,7%). Al menos se objetivó un GC en 133 pacientes (95,3%). Cuando la LDNP está indicada, ésta no debería restringirse a la exéresis de adenopatías, según la técnica de LDNP limitada o estándar, sino que tiene que realizarse siguiendo el patrón de la LDNP extendida. Hay poca experiencia con la LDNP del GC, pero todos los datos publicados hasta ahora indican que este procedimiento puede ser una alternativa a la LDNP extendida, ya que permite reducir la extensión de la LDNP sin comprometer la exactitud diagnóstica

Proper assessment of lymph node status is of crucial importance in the management of newly diagnosed prostate cancer. Early stage metastatic disease takes the form of microscopic tumor-cell deposits rather than grossly enlarged nodes. So far there is no imaging technique, however, which allows detecting small metastases in the range of a few millimetres. Therefore pelvic lymph node dissection (PLND) is the only reliable method of staging for clinically localized prostate cancer. The cornerstone of radioguided prostate surgery is a radiopharmaceutical - a carrier molecule labeled by radionuclide. After injection to at the prostate, the radiopharmaceutical crosses the lymphatic pores and migrates into the lymph vessels and from there to the first echelon of lymph nodes. We were the first to show that sentinel PLND can be performed by means of laparoscopy preceding laparoscopic radical prostatectomy. Our most recent publication presents data of 140 patients with clinically localized prostate cancer in which laparoscopic sentinel PLND was performed preceding radical prostatectomy from November 2001 to January 200514. On the preoperative scintigraphy SLNs were detected bilaterally, unilaterally, not on the pelvic-walls in 113 (80.7%), 20 (14.2%) and 6 (4.2%) patients and intraoperatively in 96 (68.6%), 36 (25.7%), 8 (5.7%) patients respectively. In 99 out of 140 patients (70.7%) intraoperatively SLN was detected in the same position as on preoperative scan. At least one SLN was detected in 133 patients (95.3%). Whenever PLND is indicated it should not be limited to lymph node sampling as provided by standard limited PLND but has to be performed in the template of extended PLND. There is only limited experience with sentinel PLND, but all the data collected so far indicate that this method has the potential to become an alternative to extended PLND since it allows for reduction of the extent of PLND without compromising diagnostic accuracy

[Laparoscopic tumor nephrectomy]. / Laparoskopische Tumornephrektomie.

Initially, laparoscopic surgery in urology was restricted to the treatment of benign diseases, whereas its role in the management of malignant disease was restricted to purely diagnostic procedures. Only recently has laparoscopy been introduced for the treatment of low stage renal cell carcinoma (RCC), and the data on both surgical efficiency and oncologic efficacy are very promising. Therefore, we present our experience with laparoscopic radical nephrectomy and data from literature. The technique of the transperitoneal approach is described in detail. Retroperitoneoscopy is a good alternative, however. Intact removal of the specimen within an organ bag to avoid tumor spillage is an important detail of our technique. Our experience amounts to radical nephrectomy in 121 patients. The indication was clinical stage T1-T2. Mean operative time and blood loss was 2.4 h and 154 ml, respectively. The rate of minor or major complications was 5% and 4%, respectively. There was no conversion to open surgery in any patient. Mean postoperative hospital stay was 6.1 days. Data on tumor control are available for 73 patients with a mean follow-up of 13.3 months. There was no recurrence within this period. Radical nephrectomy for low-stage RCC is associated with low morbidity and great surgical efficiency. The rates for local recurrences and metastases are low, tumor-specific survival is high. However, there is still a lack of long-term data on large series of patients. Despite this fact, laparoscopy is already widely accepted for this indication, and it is quite likely that it will become the standard treatment.

Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self-administration.

Extracellular dopamine and DOPAC (3,4-dihydroxyphenylacetic acid) levels in nucleus accumbens were sampled by microdialysis and quantified with high-performance liquid chromatography during intravenous heroin self-administration sessions in rats. Dopamine levels in 10 and 20 min samples were elevated following the first injection of each session, reaching a plateau of elevation within the first two or three injections and falling back toward baseline only when drug access was terminated. Elevations were in the range of 150-300% when unit dosages of 0.05-0.2 mg/kg were given. Increasing the work requirement from FR-1 to FR-10 did not appear to alter the degree of elevation of dopamine levels, and dopamine levels fell during extinction while lever-pressing rates increased 20-fold. While animals compensated for unit dose changes between 0.05 and 0.2 mg/kg/injection, adjusting their response rate such that the same hourly drug intake and the same asymptotic dopamine levels were maintained across these conditions, at 0.4 mg/kg/injection hourly drug intake and asymptotic dopamine levels were elevated beyond the levels sustained by the lower doses. These findings confirm that self-administered doses of intravenous heroin are sufficient to activate the mesolimbic dopamine system and suggest that significant heroin "craving" can emerge when dopamine levels are still moderately elevated, long before the development of dopamine depletion associated with opiate withdrawal.

Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats.

Fluctuations in extracellular dopamine and DOPAC levels in nucleus accumbens septi (NAS) were monitored in 1-min microdialysis samples taken from rats engaged in intravenous cocaine self-administration. For four rats the dose per injection was fixed at 2.0 mg/kg; for four others the dose per injection was varied irregularly, from one response to the next, between three levels (0.5, 1.0 and 2.0 mg/kg). Regardless of the dosing regimen, extracellular dopamine levels were tonically elevated by 200-800% within the cocaine self-administration periods, fluctuating phasically within this range between responses. In the fixed dose condition, the phasic increases following each injection (and the phasic decreases preceding them) averaged approximately 50% of the mean tonic elevation. Phasic fluctuations in dopamine levels remained time-locked to lever-presses even when response rate was irregular, because of the variable dose condition. In the variable dose condition greater increases in dopamine and longer inter-response times followed injections of the higher doses; dopamine fluctuations were consistent with the multiple-infusion pharmacokinetics of cocaine. DOPAC levels showed a slow tonic depression during cocaine self-administration, but individual injections were not associated with discernible phasic fluctuations of DOPAC. These data are consistent with the hypothesis that falling dopamine levels trigger successive responses in the intravenous cocaine self-administration paradigm, but inconsistent with the notion that extracellular dopamine levels are depleted at the times within sessions when the animal initiates drug-seeking responses.

Amphetamine-induced modification of quinine palatability: analysis by the taste reactivity test.

The effects of low doses of d-amphetamine (0.25-0.5 mg/kg, IP) on taste reactions elicited by quinine solutions in a 5-10-min taste reactivity test were assessed in a series of three experiments. Amphetamine consistently suppressed aversive reactions elicited by quinine solutions. The results suggest that amphetamine, like morphine, attenuates the aversiveness of the taste of quinine solution.

Psychomotor-stimulant sensitization: a unitary phenomenon?

Repeated intermittent treatment with psychomotor stimulants or opiates sensitizes animals to the locomotor activating effects of these drugs. Whereas such sensitization may have important implications for the understanding of addiction, mental illness, and the cellular basis of memory, its mechanisms remain only partially understood. Psychomotor-stimulant sensitization can result in relatively permanent changes in the response of the mesolimbic dopamine system to these agents and to a variety of stressors, but the process does not depend upon simple activation of dopaminergic neurons. Psychomotor sensitization can be produced by direct (apomorphine, bromocriptine) and indirect (amphetamine, cocaine) dopamine agonists that inhibit the firing of dopaminergic neurons and thus reduce impulse-dependent dopamine release. Moreover, some treatments that cause dopaminergic activation and dopamine (DA)-dependent locomotion fail to cause robust psychomotor sensitization. While nucleus accumbens injections of amphetamine cause DA release and enhanced locomotion, they do not sensitize the animals to subsequent systemic amphetamine. On the other hand, ventral tegmental injections of amphetamine inhibit the DA system and DA-dependent locomotion but none the less sensitize the animal to subsequent systemic amphetamine treatment. While some drugs (cocaine, amphetamine, morphine, heroin) cross-sensitize animals to each other, other drugs (bromocriptine, quinpirole) sensitize animals to themselves and each other but not to cocaine or heroin. While some cases of sensitization involve Pavlovian association of environmental cues with the drug state, others seem largely independent of such conditioning. Thus it appears that there is more than one phenomenon and more than one mechanism of psychomotor sensitization.

Effects of pimozide on the hedonic properties of sucrose: analysis by the taste reactivity test.

The ability of the neuroleptic agent, pimozide, to modify sucrose palatability was assessed using three 10-min taste reactivity test sessions. Pimozide was found to suppress the ingestive response of tongue protrusions, but enhance the mildly ingestive/neutral response of mouth movements elicited by an intraoral infusion of sucrose solution. Since the pattern of taste reactivity responding shifted from highly ingestive to mildly ingestive/neutral, our results suggest that pimozide pretreatment reduces the palatability of sucrose solution. The temporal pattern of the modification of these taste reactivity responses was predicted by the Anhedonia Hypothesis.

Ramsey's Theorem for a Class of Categories.

Ramsey's Theorem states that for a sufficiently large set S, and for any splitting of the k-element subsets of S into r classes, there is a subset T [unk] S, [unk]T[unk] = l, such that all k-element subsets of T are in the same class. This paper establishes a theorem for certain categories that generalizes Ramsey's Theorem. In particular, it is strong enough to establish G-C. Rota's conjecture that the vector space analogue to Ramsey's Theorem is true. It also implies the Ramsey theorem for n-parameter sets, which has as corollaries, among others, the theorem of van der Waerden on arithmetic progressions and several results of R. Rado on regularity in systems of linear equations.