Evaluation of the pathologic response to neoadjuvant treatment in rectal cancer. Experience at the Instituto de Cancerología de Medellín (Colombia, 2011-2017). / Evaluación de la respuesta patológica al tratamiento neoadyuvante en cáncer de recto. Experiencia del Instituto de Cancerología de Medellín (Colombia, 2011-2017).

INTRODUCTION AND AIMS: Neoadjuvant therapy in rectal cancer is associated with a decrease in tumor size and is the therapeutic indication for patients with T3 or T4 tumors or lymph node involvement. Our aim was to describe the frequency of pathologic response and the survival rate in patients that underwent neoadjuvant therapy for rectal cancer. MATERIALS AND METHODS: A retrospective follow-up study with a survival analysis was conducted. Patients with locally advanced rectal cancer that received neoadjuvant treatment and were operated on at the Instituto de Cancerología Las Américas (Medellín, Colombia) were analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: A total of 152 patients were included. Mean patient age was 59 years (12.8 SD), 53.9% were men, and 58.6% of the patients were diagnosed with stage IIIB disease. The pathologic complete response (pCR) was achieved in 17% of the patients. A total of 146 (96.1%) patients received the chemoradiotherapy protocol. Fifty-two (34.2%) patients developed metastasis and/or relapse, and one (3.8%) of those patients had presented with pCR. The median follow-up period was 33 months (Q1-Q3: 20-45), with an overall survival rate of 79.5% (95% CI 70.9-85.8). The 5-year survival rate for the patients that had pCR was 80% (95% CI 20.3-96.9). CONCLUSIONS: The frequency of pCR was similar to that in other published studies and disease recurrence was lower, compared with patients with no response. The 5-year survival rate in patients with pCR was high, albeit lower than that reported in other studies.

Ferritina plasmática materna en el tercer trimestre del embarazo y crecimiento fetal / Maternal plasma ferritin during the third trimester of pregnancy and foetal growth

Objetivo: Relacionar las concentraciones de ferritina plasmática materna en el tercer trimestre del embarazo con el crecimiento fetal. Materiales y métodos: Se seleccionaron pacientes con embarazos simples en el tercer trimestre que presentaron partos a término y que fueron atendidas en el Hospital Central «Dr. Urquinaona», Maracaibo, Venezuela. Se evaluaron la edad materna, edad gestacional al momento de la toma de la muestra y del parto, valores de hematocrito, concentraciones plasmáticas de ferritina materna y peso del recién nacido. Resultados: Se seleccionaron 131 pacientes embarazadas en el tercer trimestre a las cuales se les pudo realizar las mediciones de ferritina. La edad promedio de las pacientes fue de 30,6±4,1años. Las concentraciones promedio de ferritina fueron de 31,7±14,7ng/dl y el peso promedio de los recién nacidos fue de 3.194±434g. Al dividir las concentraciones de ferritina materna en cuartiles (concentraciones bajas, medias, altas y muy altas), se observó que las pacientes con concentraciones muy altas y altas de ferritina materna tenían recién nacidos con pesos significativamente más bajos que las pacientes con concentraciones bajas de ferritina (p<0,001). Se observó una correlación moderada, negativa y significativa entre la concentración de ferritina materna y el peso de los recién nacidos (r=-0,481; p<0,001). Conclusión: Existe una relación negativa y significativa de las concentraciones de ferritina plasmática materna en el tercer trimestre del embarazo con el crecimiento fetal

Objective: To relate maternal plasma ferritin concentrations during the third trimester of pregnancy to foetal growth. Materials and method: Patients with single pregnancies in the third trimester who had term deliveries and were cared for at the Hospital Central 'Dr. Urquinaona', Maracaibo, Venezuela were selected. Maternal age, gestational age at moment of sample and delivery, haematocrit values, maternal plasma ferritin concentrations and birth weight were evaluated. Results: We selected 131 patients in the third trimester of pregnancy in whom ferritin measurements could be performed. The mean age of the patients was 30.6±4.1 years. The mean ferritin concentration was 31.7±14.7ng/dl and the mean birth weight of the newborns was 3,194±434g. When the ferritin concentrations of the mothers were divided in quartiles (low, medium, high and very high concentrations), it was apparent that patients with very high and high concentrations of ferritin had newborns with significant lower birth weight than patients with low concentrations of ferritin (P<.001). A moderate, negative and significant correlation between maternal plasma ferritin concentration and newborn birth weight was also observed (r=−.481; P<.001). Conclusion: There is a negative and significant relationship between maternal plasma ferritin concentrations during the third trimester of pregnancy and foetal growth

Linfoma de células B de la zona marginal extranodal del tejido linfoide asociado a mucosas (malt) primario de esófago: Presentación de un caso

El tracto gastrointestinal es la localización mas frecuente de los linfomas no Hodgkin extranodales, sin embargo, el compromiso del esófago es extremadamente raro, con una incidencia menor del 1% de todos los pacientes con linfoma. Se ha descrito con mayor frecuencia afectación secundaria del esófago como parte de un compromiso extenso de un linfoma gástrico o mediastinal. Se presenta el caso de paciente femenina, de 59 años de edad, con síntomas dispépticos de 2 meses de evolución. En la Endoscopia Digestiva Superior (EDS) se evidencia en tercio distal de esófago, lesión elevada, de 1cm de diámetro, con características similares al resto de la mucosa, móvil. La biopsia Endoscópica revela la presencia de un linfoma MALT de bajo grado confirmado por inmunohistoquímica. Se indicó tratamiento de erradicación para H pylori, y los estudios de extensión fueron normales. Posteriormente se realizó resección mucosal endoscópica, donde se observaron grupos aislados de linfocitos neoplásicos, con bordes de resección libres. Paciente con seguimiento endoscópico normal. Pocos casos han sido reportados en la literatura acerca de linfomas MALT de esófago, por lo tanto las características clínicas y biológicas de estos linfomas no están claramente establecidas. Es necesario el estudio y seguimiento de estos casos, para determinar los posibles factores de riesgo y así aplicar las medidas preventivas.

The gastrointestinal tract is the most common extra nodal site involved in Non- Hodgkin's lymphoma. However, esophageal involvement is extremely rare, accounting for less than 1% of patients with lymphoma. It has been described that esophageal involvement in lymphoma is more often a result of contiguous spread from mediastinal lymph nodes or from an extended gastric lymphoma. A 59 year old female consulted for dyspeptic symptoms. Endoscopic examination revealed a small submucosal mass, that measured 1 cm located at the lower thoracic esophagus. The biopsy reported a Malt lymphoma that was confirmed by immunohistochemistry. She received therapy for H. pylori eradication. Endoscopic mucosal resection was performed, and isolated groups of atypical lymphocytes were found, with free resection margins. Endoscopic follow up has been normal. Few cases have been reported in literature, therefore biological and clinical characteristics of MALT lymphoma of the esophagus are currently unknown, further study is needed to establish risk factors in order to be able to take preventive measures.

Carcinoma gástrico precoz mucinoso: Reporte de un caso y revisión de la literatura

El carcinoma gástrico mucinoso (CGM) es infrecuente representa el 3% de todos los canceres gástricos (1). Detectado ocasionalmente en estadios precoces (2), con una relación avanzados/precoces de 2.1 - 2.3% y 0.3 - 1.0% respectivamente (1, 2). Correspondiendo el CGM en estadio precoz al 0.02 de todos los carcinomas gástricos. Se reporta este inusual caso de paciente femenina de 72 años de edad quien consultó por síntomas dispépticos, se hizo el diagnóstico histológico de ADC gástrico, por biopsia endoscópica, siendo sometida a gastrectomía subtotal, y cuyo reporte definitivo de la pieza quirúrgica fue CGM precoz, con compromiso submucoso, sin evidencia de ganglios metastáticos.

Mucinous gastric cancer (MGC) is very rare. The incidence of MGC is about 3% among all gastric cancers and only occasionally detected in early -stage with a relation between advanced and early gastric cancer around 2.3- 21% and 0.3- 1% respectively. Early-stage mucinous gastric cancer represents 0.02 of all gastric cancer types. We report an unusual case of a 72 years old female patient with histological diagnosis of gastric Adenocarcinoma. A total gastrectomy was performed. Final diagnosis was that of an early mucinous gastric cancer involving the submucosal layer without lymph node metastasis.

Effect of the cerebral tryptaminergic system on the turnover of dopamine in the striatum of the rat.

The effect of the cerebral 5-hydroxytryptamine system on the turnover of striatal 3,4-dihydroxyphenyl-ethylamine (dopamine) was investigated by measuring the level of dopamine and one of its metabolites in rats depleted of cerebral 5-hydroxytryptamine or treated with a 5-hydroxytryptamine receptor blocker. Treatment with p-chlorophenylalanine induced, in addition to a reduction in striatal 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid, an increase in the striatal concentration of dopamine, a diminution in the concentration of homovanillic acid in the same cerebral area, and a reduction in the rise of this acid after the administration of a butyrophenone derivative or tetrabenazine. Treatment with methysergide also reduced the increase of homovanillic acid induced by the butyrophenone. When probenecid was given to rats treated with p-chlorophenylalanine, homovanillic acid failed to accumulate, whereas the accumulation of 5-hydroxyindol-3-ylacetic acid was unaffected. The decay of dopamine after alpha-methyl-p-tyrosine administration was normal for the first 6 h but was later reduced in rats given p-chlorophenylalanine or methysergide. The results suggest that the lack of activation of 5-hydroxytryptamine receptors leads to a reduction in the turnover of dopamine in the nigrostriatal pathway.

The effect of fasting on 5-hydroxytryptamine metabolism in brain regions of the albino rat.

The turnover of 5-hydroxytryptamine (5-HT) in the whole brain and different brain regions was studied in rats fasted for 24 h. These rats showed an increased tissue concentration of the amine in the whole brain and of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the whole brain, the striatum, the combined pons-medulla and the cerebral cortex. The accumulation of 5-HIAA after probenecid was increased by fasting in the regions mentioned above except for the striatum. The effect of probenecid was also increased by fasting in the midbrain, the hypothalamus and the hippocampus. In the striatum, the administration of probenecid produced a smaller increase in 5-HIAA concentration in fasted than in fed rats. The decay of 5-HT following p-chlorophenylalanine (PCPA) was increased in the hypothalamus of fasted rats at 16 h, but not at 4 h, after the intraperitoneal administration of the inhibitor. In the midbrain, the striatum and the combined pons-medulla, food deprivation did not modify the decrease induced by PCPA. However, the inhibitor induced a reduction of food consumption in the fed group, which made this group rather similar to the fasted one and complicated the interpretation of the results in these last three cerebral areas. Our results confirm that food deprivation increases the turnover of brain 5-HT and point out that the increase probably occurs in all brain areas. This increased turnover appears to be accompanied, in the hypothalamus, by an increased neuronal release of the amine. In the striatum, fasting probably blocks the active transport system which removes acid metabolites from the brain.

Factors influencing the cholinesterases of cerebrospinal fluid in the anaesthetized cat.

Both acetylcholinesterase and non-specific cholinesterase are found in cerebrospinal fluid and blood plasma of the cat; the ratio of activities acetylcholinesterase/non-specific cholinesterase is about 1.5 in cerebrospinal fluid and 0.15 in plasma. A search was made for factors capable of influencing the concentration of the two cholinesterases in cerebrospinal fluid. Either the ventricular system was perfused with artificial cerebrospinal fluid from a lateral ventricle to the aqueduct, or the atlanto-occipital membrane was punctured and cerebrospinal fluid was collected continuously from the cisterna magna. Factors studied included: (a) procedures affecting the composition or formation of cerebrospinal fluid, such as changes in the ionic constituents of the perfusate, the inhibition of cerebrospinal fluid formation by acetazolamide or ouabain, or the rapid intra-carotid infusion of hypertonic urea; (b) arousal (noise or stimulation of the central ends of the sciatic nerves), or deepening of anaesthesia; (c) changes in blood pressure; (d) central stimulants and depressants, pyrogens, prostaglandins, antagonists of acetylcholine. Whereas most procedures or drugs tested increased the concentration of acetylcholinesterase, some central depressants (e.g. chlorpromazine) reduced, while another (ether) increased the appearance of acetylcholinesterase in the cerebrospinal fluid. The effect of ether was, in all probability, due to damage to the blood-brain barrier. A rise in acetylcholinesterase concentration was obtained upon stimulation of the central ends of the sciatic nerves; this was inhibited by atropine but not by N-methylatropine, indicating that the rise was due to increased nervous activity and not to the circulatory effects of the stimulation, since the changes in blood pressure caused by the stimulation remained the same after atropine administration. Amphetamine or leptazol raised the levels of acetylcholinesterase but it was not possible to determine whether this was due only to increased central nervous activity, since there was invariably leakage through the blood-brain barrier which by itself would be sufficient to produce the effect. A rise in the level of acetylcholinesterase was seen after administration of pyrogen; this was apparently not a simple effect of warming the body, but due to the action of the pyrogen on centers concerned with temperature control, since warming the animal by external heat failed to produce a similar change.(ABSTRACT TRUNCATED AT 400 WORDS)

An in vivo cholinergic influence on the retention of [3H]noradrenaline in regional brain synaptosomes.

Rats were intraventricularly (icv) injected with [3H]noradrenaline and the retention of the amine was determined in synaptosomes obtained from cerebral cortex, hypothalamus and brain stem. Previous icv administration of hemicholinium-3, effective enough to markedly decrease brain acetylcholine levels, increased the retention of synaptosomal [3H]noradrenaline in hypothalamus and cerebral cortex; this increased retention did not occur in the brain stem. The increased retention of [3H]noradrenaline, produced by hemicholinium-3, was reversed by a concomitant icv dose of choline, which in turn reversed the decrease of acetylcholine caused by hemicholinium-3. These results are interpreted as brain cholinergic activity having an influence on the turnover of noradrenaline in some brain regions.

The effect of fasting on the stereotyped behaviour induced by amphetamine and by apomorphine in the albino rat.

Fasting increases the synthesis and metabolism of cerebral 5-hydroxytryptamine and modifies dopamine turnover in the striatum. We studied the effect of a 24 h fast on the motor hyperactivity induced by amphetamine or by apomorphine. Locomotion was evaluated in photocell cages and stereotypy by direct observation and the use of rating scales. Amphetamine, 2.0 mg/kg, induced and increase in locomotion with a maximum between 20 and 30 min of its injection. After 40 min there was a decay in the amphetamine effect but the reduction was significantly smaller in the fasted than in the fed rats. Haloperidol, 0.025 mg/kg, abolished the decay of the amphetamine effect mentioned above and also eliminated the difference between fasted and fed rats. The stereotypy effect of amphetamine was of similar intensity in both groups during the first 30 min after the injection. After 40 min however, fasted rats developed a less intense stereotypy effect than did fed rats. Haloperidol induced a pronounced reduction of stereotypy in both groups and abolished the difference between fasted and fed rats. The stereotypy effect of apomorphine was unaffected by fasting. We suggest that food deprivation reduces the stereotypy effect of amphetamine by acting at a presynaptic dopaminergic level in the striatum.

The influence of cerebral 5-hydroxytryptamine on catalepsy induced by brain-amine depleting neuroleptics or by cholinomimetics.

1 Catalepsy was produced in rats and mice by the subcutaneous injection of either tetrabenazine or the butyrophenone U-32,802A (4'-fluoro-4-{[4-(p-fluorophenyl)-3-cyclohexen-1-yl]amino} butyrophenone hydrochloride). Catalepsy was evaluated by the duration of total immobility on a vertical grid.2 Pretreatment with p-chlorophenylalanine (PCPA) reduced the intensity of catalepsy by 50% or more, whereas its time course remained the same.3 5-Hydroxytryptophan (5-HTP), 10 mg/kg, enhanced the catalepsy induced by U-32,802A or tetrabenazine, provided it was administered soon (45 min) after the neuroleptic; injections at 90 min had no effect. Otherwise untreated rats given this dose of 5-HTP behaved normally on the grid.4 The anticataleptic effect of PCPA was reversed by 5-HTP.5 Measurable changes in 5-hydroxytryptamine (5-HT) metabolism in the rat forebrain accompanied the modification of catalepsy by 5-HTP and PCPA.6 Methysergide (5 mg/kg) given 30 min before the neuroleptics to either mice or rats reduced the catalepsy, assessed 2.5 h after the methysergide. It also prevented the increase in neuroleptic-induced catalepsy following 5-HTP, 10 mg/kg.7 Tryptophan, like 5-HTP, increased the catalepsy seen in mice after U-32,802A and tetrabenazine, and increased the production of 5-hydroxyindol-3-ylacetic acid in the forebrain.8 In the rat, intracerebroventricular injection of physostigmine produced catalepsy which was not modified by methysergide or PCPA but was abolished by atropine. Similarly, in the mouse, catalepsy induced by the subcutaneous injection of pilocarpine was abolished by atropine but not affected by either methysergide or 5-HTP.9 Atropine greatly reduced the catalepsy induced by U-32,802A and tetrabenazine but lowered striatal homovanillic acid (HVA) only after U-32,802A. D,L-DOPA, 20 mg/kg, diminished the cataleptogenic effect of both neuroleptics and raised striatal HVA.10 The results support the view that there is a facilitating or permissive action of 5-HT-containing neurones on neuroleptic-induced catalepsy.

Production of catalepsy and depletion of brain monoamines by a butyrophenone derivative.

1 The cataleptic and monoamine-depleting effects of a butyrophenone derivative (4'-fluoro-4-[[4-(p-fluorophenyl)-3-cyclohexen-1-yl]-amino]-butyrophenone hydrochloride, U-32, 802A) were studied in rats and mice and compared with those of tetrabenazine. 2 Catalepsy was evaluated by means of a modified grid test which allowed the repetition of the test in the same animal several times without affecting the results. Both drugs produced a dose-related cataleptic state of similar time course. 3 Like tetrabenazine, U-32, 802A induced a large reduction in the content of 5-hydroxytryptamine, dopamine and noradrenaline in different parts of the brain, with a concomitant elevation in the metabolites 5-hydroxyindol-3-yl acetic acid and homovanillic acid. The time courses of the catalepsy and the reduction in brain monoamines were very similar. 4 The activity of U-32, 802A suggested that the drug, although chemically a butyrophenone, might act primarily at the presynaptic organelle for storage of monoamines in a way similar to tetrabenazine.

Presence of serotonin in the rat vas deferens: its influence on contractile responses.

Serotonin has been detected in the rat vas deferens. Increase in the serotonin concentration by exposure of the rat vas deferens to L-tryptophan occurs in vitro. p-chlorophenylalanine partly blocks the increase in serotonin concentration induced by tryptophan in vitro but not in vivo. Chronic sympathetic denervation induces an increase in 5-HT concentration. Responses of the vas deferens to transmural stimulation are depressed by pretreatment of rats with p-chlorophenylalanine, and the depression is reversed by incubation in vitro with 5-hydroxytryptophan or serotonin. Serotonin can enhance the response to transmural stimulation at low concentrations but has no effect at higher concentrations. Physostigmine-induced enhancement of the response to stimulation is depressed only by higher concentrations of serotonin. The results raise the question whether endogenous serotonin can act as a modulator of neurotransmission in the rat vas deferens.

PIP: Various experiments were conducted to evaluate the influence of serotonin (5-HT) on contractile responses of the rat vas deferens in vitro and in vivo. In vitro exposure of the vas deferens to L-tryptophan increased serotonin concentration. p-Chlorophenylalanine partially blocked this increase in vitro but not in vivo. The concentration of 5-HT was also increased by chronic sympathetic denervation. Pretreatment with p-chlorophenylalanine depressed the contractile response to transmural stimulation, while incubation with 5-hydroxytryptophan or serotonin reversed this effect. Low, but not high, concentrations of serotonin enhanced the response to transmural stimulation. However, only high concentrations of serotonin depressed the physostigmine-induced enhancement of the contractile response to transmural stimulation. The results suggest that endogenous serotonin may modulate neurotransmission in the rat vas deferens.