Cerebellar mutism syndrome: the importance of preoperative language assessment.

Children undergoing surgical removal of tumors in the posterior cranial fossa can encounter a varied and complex constellation of neurological symptoms, called cerebellar mutism, defined as a disturbance in the planning and programming of motor language with preserved understanding, behavioral disorders such as inattention, visual-spatial disorganization, personality change, as well as ataxia and dysmetria. In the last years, several groups have been trying to establish risk factors or even predictive scores in order to be able at least in part to predict the appearance of speech disorders before surgery. We report on a child with pilocytic astrocytoma of the cerebellar vermis who had already been diagnosed with developmental linguistic delay two years earlier. This disorder initially worsened after surgery and later improved in the following 12 months. The aim of this paper is to emphasize the importance of preoperative neuropsychological evaluation. The present case, along with those reported in the literature, suggests that the risk of long-term cerebellar mutism is higher in children with preoperative speech disorders. In these patients a thorough assessment of cognitive and linguistic functions is therefore necessary to better evaluate the risk of cerebellar mutism after surgery.

Language testing in brain tumor patients.

Neuropsychological testing is not a luxury in the management of patients with brain tumors. Regardless of the therapeutic approach selected in each case (but, especially in the case of awake surgery), it provides information on the status of language and other cognitive functions. This information can be used preoperatively to identify eloquent areas and to provide a baseline against which further examinations can be evaluated, intraoperatively to identify eloquent areas, and post-operatively and at follow-up to ascertain the short-term and long-term consequences of surgery, as well as those of other treatments (chemotherapy and radiotherapy), and to plan and monitor rehabilitative treatments.

Cognitive outcome as part and parcel of clinical outcome in brain tumor surgery.

Although validated tools (neuropsychological tests, patient reported outcomes, mood and psychological profile) were first introduced many years ago in clinical practice, the impact of the tumor itself on patient cognition has not been extensively studied. Furthermore, while outcome research is evolving in an attempt to adapt the use of different tools to the preoperative and postoperative phases, the standard guidelines for evaluating outcome after brain surgery, by neurological examination and complication assessment, are frequently neglected in the current literature. This article attempts to provide an appraisal of the evidence for the impact of surgical treatment on cognitive function of brain tumor patients within the context of general outcome.

Cognitive outcome after awake surgery for tumors in language areas.

In surgery for tumors of the dominant hemisphere, the attention devoted to quality of resection and preservation of language function has not been accompanied by comparable interest in preservation of cognitive abilities which may affect quality of life. We studied 22 patients undergoing awake surgery for glioma removal in the language areas of the brain. Besides monitoring tumor variables (size, location, histology, edema), we used a multifaceted battery of tests to investigate mood, cognition, and language in an attempt to assess the burden of disease and treatment, and the relationships between these three dimensions. Baseline assessment showed that 45% of the patients were depressed and 23% anxious; some cognitive and language impairment was noted for 59 and 50%, respectively. A general decline in postoperative cognitive performance (significant for memory and attention only) and language function (significant for picture naming) was observed, whereas depression was unchanged and anxiety decreased. Tumor histology, but not demographic variables or extent of resection, correlated with postoperative cognitive changes: patients undergoing surgery for high-grade tumors were more likely to improve. No correlation was observed between scores for mood, cognition, and language function. A subset of patients with low-grade glioma was followed up for 3-6 months; although some improvement was observed they did not always regain their preoperative performance. In conclusion, we believe that cognitive assessment performed in conjunction with language testing is a necessary step in the global evaluation of brain tumor patients both before and after surgery.

Isolated liver transplantation in an infant with ultrashort gut.

Intestinal function in children with very short bowel syndrome and related intestinal failure may improve after isolated liver transplantation. An infant with an ultrashort gut, ileo-cecal valve, and whole colon received total parenteral nutrition from the first days of life. Enteral feeding failed because of the progressive dilatation of the jejunal portion and motility disorders. He developed early severe cholestatic liver disease (aspartate transferase 186, alanine transferase 103 U/L, serum bilirubin 8.4 mg/dL) and subsequent liver failure. At 8 months of age, he benefited from isolated liver transplantation (left segment graft from living donor). His early posttransplant evolution was characterized by recovery of oral alimentation, improvement of digestive and absorption functions, but he did not achieve TPN-independence. At 20 months, 50% to 60% of his energy needs were covered by parenteral nutrition and he has satisfactory growth indices (3rd percentile for weight and height), reduced stool volume, and frequency. Isolated liver transplantation allowed, in this particular case, time for further intestinal adaptation thereby avoiding the need for intestinal transplantation early in life.

Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis.

BACKGROUND: Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. AIMS: To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. PATIENTS: Patients with pancreatic exocrine insufficiency due to cystic fibrosis. METHODS: Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. RESULTS AND CONCLUSIONS: Of the 33/60 patients who expressed a preference for one of the two treatments, 30 preferred Creon while only 3 patients preferred Pancrease (p<0.001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon. The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease.

[Pancreatic extract therapy in exocrine pancreatic insufficiency]. / La terapia con estratti pancreatici nell'insufficienza pancreatica esocrina.

The authors consider the different strategies in long term enzyme replacement therapy in relation to the complex mechanics at the basis of pancreas exocrine insufficiency. This condition occurs in chronic pancreatitis and is present in Cystic Fibrosis, the most common potentially lethal inherited disorder of Caucasians. Pancreatic exocrine insufficiency occurs in the vast majority of cystic fibrosis affected children and is now becoming a frequent pathology in adults for the better life expectancy and the recent acknowledgements in this disease. The principal aims of research in enzyme replacement therapy have been directed at the formulation of products with high enzyme concentration, to the prevention of gastric acid inactivation of enzymes and to the better mixing of the preparations with meals. The authors consider all the different enzyme preparations from pancreatin powder to the 1st. generation of enteric coated tablets and examine the advantages of administering H-2 receptor antagonists or antacids and the possibility of stimulating bicarbonate secretion as an adjunct to pancreatic enzyme replacement therapy. Significant benefits in pancreatic insufficiency therapy have derived from the introduction of enteric coated microspheres which ensure a consistent level of enzymes to reach the duodenum mixed with the meal and which are resistant to gastric acid inactivation as well.

Serum group I pepsinogens level in cystic fibrosis.

Fasting serum pepsinogen 1 level was determined by radioimmunoassay in 30 patients with cystic fibrosis and in on equal number of age-matched healthy children. Serum pepsinogen 1 basal levels were significantly higher (49 +/- 18 ng/ml; p less than 0.01) in cystic fibrosis patients than in controls (38 +/- 12 ng/ml). The increased pepsinogen 1 level did not correlate with the levels of Po2 and Pco2 tensions, fat balance or basal and maximum acid outputs. It is concluded that the mechanisms which lead to a rise of serum pepsinogen 1 in cystic fibrosis are unknown. However these findings could provide useful information with regard to the biology of a disease whose physiopathology is still unknown.

[Cystic fibrosis: molecular genetics and new perspectives of prevention and therapy]. / Fibrosi cistica: genetica molecolare e nuove prospettive di prevenzione e terapia.

Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder among Caucasians, occurring with a frequency of 1/2000 newborn babies. This editorial will consider the clinical features of CF as well as the genomic structure of the CFTR gene and the functional properties of its product, mutations of the gene, correlations between genotypes and phenotypes, strategies for carrier screening, and recent advances in gene therapy. After isolation and cloning of the CFTR gene, different laboratories have characterized over 350 mutations responsible for CF, the most frequent being the delta F508 which accounts for 70% of all CF chromosomes. Studies on correlations between genotypes and phenotypes have confirmed that patients with the homozygous delta F508/delta F508 genotype are severely affected, with major involvement of pancreatic function. Patients with the delta F508/R117H genotype, on the other hand, evidence a mild phenotype with pancreatic sufficiency. Several pilot studies for carrier detection are now in progress. As recent experiments with somatic gene therapy, performed on knock-out mice for the CFTR gene have given satisfactory results, it is hoped that the same approach can soon be used for humans.

[Vitamin E: physiology and pathology]. / Vitamina E: fisiologia e patologia.

The purpose of this report is to present an overview on vitamin E distribution, requirements, absorption and biochemical and nutritional aspects. A continuous interest in biochemical functions is recently developed and vitamin E certainly plays an important role throughout the body. The best known of its effects and still actively considered in recent years is the role as an important biological antioxidant. The red blood cell is an ideal model for studying the antioxidant role of vitamin E in cell membranes. Nutritional deprivation is a rare occurrence in developed countries. In prematurely delivered newborns the deficiency is due to marginal stores and to transient malabsorption but it can also be iatrogenic. In infants and adults vitamin E deficiency does occur in syndromes characterized by increased consumption or reduced absorption. Various gastrointestinal disorders induce, with steatorrhoea, marked alteration of vitamin E levels. Cystic fibrosis (CF), the commonest cause of pancreatic insufficiency during the first decades of life, is of particular interest. The fat malabsorption, often severe, may not well respond to pancreatic therapy and the hepatobiliary disease, increased in frequency with improved survival, induce a further reduction in intestinal bile salt concentration. Several manifestations have been attributed to vitamin E deficiency in CF and, although overt neurological complications seem to be relatively uncommon, it is recommended to maintain an adequate supplementation.

[Advantages and limits of rigid rectosigmoidoscope and flexible colonoscope in childhood]. / Vantaggi e limiti del rettosigmoidoscopio rigido e del coloscopio flessibile nell'esplorazione del rettocolon in età pediatrica.

During the past ten years 220 pediatric proctosigmoidoscopies with the rigid instrument in 182 infants and children, and 71 colonoscopies in 62, were performed. Advantages and limits of these two instruments are discussed. The indications and results of the different procedures are presented. Positive diagnoses were obtained in 81% with both techniques while the histological examination was positive in 85% of specimens obtained by colonoscopy and only in 51% of the proctosigmoidoscopical ones. Colonoscopy has increasingly became a complementary method for colonic pathology in children, in comparison with adult medicine, however, pediatric indications have been handled mostly with the shorter instrument for two main reasons: 1) Pediatric colonic pathology affects predominantely the lower tract; 2) Neoplastic lesions, in which total colonoscopy with biopies at different levels is mandatory, are extremely rare in children.

[Therapy of pancreatic insufficiency]. / Terapia dell'insufficienza pancreatica.

The replacing therapy in the treatment of pancreatic insufficiency is considered the first and most important step. At present, the choice is between highly concentrate or enteric-coated enzymatic compounds. Their administration before or during each meal has to be the one able to reduce fecal fat and nitrogen, allowing a satisfactory growth. A long term therapy even at low dosage with antacids or cimetidine must be considered with caution and evaluated in each case. In CF children the nutritional care has now been emphasized for the possible relationship between malnutrition and lung disease; the caloric intake must be higher than normal. The limitation of fat intake is not so important any more when the enzymes replacement is adequate. The vitamins requirement is usually satisfied doubling the normal daily requirement. An increase of vitamins and/or minerals must be considered when clinical or laboratory signs of deficiency are found.

[Behavior of pepsin in childhood and its correlation with gastric acid secretion]. / Comportamento della pepsina nell'infanzia e sue correlazioni con la secrezione acida gastrica.

Little attention has been given to the gastric secretion of pepsin in children. The purpose of this paper is to define the behaviour of peptic concentration (UI/ml) and Basal (BPO) and Stimulated (SPO) Peptic Outputs in children with normal and altered gastric acid secretion. 54 children, aged 15 months to 12 years, were studied: 20 of them were normal, 20 had gastric hypersecretion and 14 were hyposecretors. In the normal subjects the BPO is inversely correlated with age, while the SPO increases with the body weight, but this increment diminishes after the age of 6 years. From these data one can assume that the gastric principal cells reach their functional maturity around the age of 6 years. In the hypersecretors peptic and acid secretions are not correlated in basal conditions, while after pentagrastrin stimulation peptic secretion is greater than in normal subjects but not as the acid one. The SPO is correlated with body weight and height. The different behaviour of hydrochloric acid and pepsin is probably due to the use of pentagrastrin, which is a specific stimulant of oxyntic but not of principal cells. In the hyposecretors both BPO and SPO are lower than in normal children and no correlation was found with age, body weight and acid secretion.

[Irritable bowel syndrome in children]. / La sindrome dell'intestino irritabile nell'infanzia.

The irritable bowel syndrome (IBS) is the most common chronic functional gastroenterological disorder both in adults and in children. In this study we evaluate the different aspects of this syndrome, comparing our observations on 332 children with other studies. Epidemiological data (frequency, sex, age) are examined so as the family histories of gastroenterological disorders. We take in account several pathogenic hypotheses, especially with reference to the alterations of gastrointestinal motility, which could be caused by several factors (psychological, prostaglandins, bile acids, etc.). The clinical picture is very variable, variations depending on the age of children and on the time of onset of IBS. The colic of neonate, caused by retention of air, is the main symptom in the first months of life, followed by chronic diarrhoea, also defined as toddler's diarrhoea, sometime alternating with constipation. In later childhood, recurrent abdominal pain represents a common complaint, in association with diarrhoea or constipation. The principal steps for a proper diagnosis so as the main differential diagnosis are defined. We explain the most important features of management (reassuring parents, free diet), excluding prescription of drugs, that produce only a transitory and symptomatic relief, so as elimination diets, that cause only a failure to thrive without any improvement of symptoms.

A randomized placebo-controlled study on high-dose oral algal docosahexaenoic acid supplementation in children with cystic fibrosis.

Low plasma concentrations of docosahexaenoic acid (DHA) are reported in unsupplemented cystic fibrosis (CF) patients. Forty-one CF patients aged from 6 to 12 years were randomized to receive high-dose DHA (100 mg/kg/day in the first month and 1g per day thereafter through a 12-month supplementation) or placebo (germ oil). Primary outcome was percentage change in plasma AA:DHA ratio. Secondary outcomes were changes in the number of pulmonary exacerbations compared to previous year, lung function, BMI, skinfold thicknesses, and body composition assessed by DXA and in serum concentrations of C-reactive protein, cytokines and vitamin (α-tocopherol and retinol). Compared to the control group plasma AA:DHA ratio decreased in the intervention group after 6 months (median percentage changes: -73% in the intervention group vs. -10% in the control group, P=0.001). No differences were detected between groups for secondary outcomes. Despite a decrease of the AA/DHA ratio, DHA supplementation for one year did not induce any significant biochemical and clinical improvement in CF patients.

El papel de la radioterapia en el tratamiento del cáncer de ovario: revisión de la literatura / The role of radiotherapy in ovarian cancer: literature review

Múltiples revisiones han estudiado el potencial coadyuvante en la radioterapia (RT) y quimioterapia (QT) en el tratamiento del cáncer de ovario, pero no se ha comparado adecuadamente la efectividad de la RT abdominal total (RTAT) versus nuevas drogas de QT. Tanto la cirugía como la QT previas a la RT aumentan la sobreviva total y libre de enfermedad, ya que radiosensibilizan al tumor favoreciendo su destrucción. Las distintas técnicas de RTAT no han demostrado diferencias significativas en la sobrevida ni en el control de la enfermedad, pero la RTAT de campos abierto si arrojó menor toxicidad tardía. En la actualidad nuevas técnicas como la IMRT (radioterapia de intensidad modulada) han comenzado a utilizarse con excelentes resultados. A pesar de los avances, muchos de estos pacientes desarrollan recurrencia intraabdominal, quedando fuera del rango terapéutico para QT y en dicho momento la RT puede ser utilizada también en forma paliativa con dosis grandes y únicas, cuidando la aparición de posibles complicaciones. Es probable que en el futuro se reintegre la RTAT en el tratamiento del cáncer de ovario de acuerdo a los hallazgos en el acto operatorio. Finalmente la RT/QT concomitantes, han demostrado su efecto sensibilizador sinergista y es esperable que con el tiempo se sigan integrando nuevas drogas con distintas interacciones como los taxanos y moléculas target. El tratamiento del cáncer de ovario sigue siendo esencialmente quirúrgico y con quimioterapia adyuvante, sin embargo también la radioterapia con quimioterapia han demostrado su efecto adyuvante. A pesar de ser una alternativa poco explorada en la actualidad es necesario estudiar prospectivamente el promisorio resultado de las nuevas técnicas de radioterapia en este tipo de pacientes.

Several studies have reviewed the potential coadjuvant of Radiotherapy (RT) and chemotherapy in the treatment of ovary cancer. However the effectiveness of total abdomen RT (RTAT) versus new QT drugs have not been adequately compared. Both surgery and QT prior to RT increase total and freedom from the disease since tumors become radiosensitive, thus favoring destruction. Diverse techniques such as IMRT (Intensity modulated radiation therapy) are being used with excellent results. Despite these advances, many of the patients develop intrabdominal recurrence leaving them out of the therapeutic scope/range for QT. RT may then be used as a palliative in big unique cases watching possible complications. RTAT may eventually be restarted in the treatment of ovary cancer depending on the findings during surgery. Finally, RT/QT concomitants have shown their effect in sensitivity and synergy and it is expected that new drugs with different interactions such as taxan and target molecules are added. Treatment of ovarian cancer remains essentially surgical and with chemotherapy, but both radio and chemotherapy has demonstrated their adjuvant effect. Despite being an unexplored alternative is necessary to study prospectively the promising results of new techniques of radiation therapy in these patients.

Radioterapia lumboaórtica en pacientes con cáncer de cuello uterino: experiencia del Instituto Nacional del Cáncer / Paraortic radiotherapy in patients with uterine cervical carcinoma: Instituto Nacional del Cáncer experience

Antecedentes: El cáncer de cérvicouterino continúa siendo una enfermedad prevalente en Chile. Es frecuente recibir pacientes en etapas IIB y IIIB donde el riesgo de compromiso ganglionar pelviano y lumbo-aórtico es elevado y el tratamiento es radioquimioterapia. Objetivo: Análisis retrospectivo de pacientes con cáncer cérvicouterino que recibieron radioterapia que incluía los territorios lumboaórticos. Método: Revisión de pacientes con cáncer cérvicouterino tratadas entre 1995 y 2007 en el Instituto Nacional del Cáncer, Santiago, Chile. En 39 pacientes el tratamiento incluyó las cadenas lumboaórticas. Se analizó toxicidad y evolución. Se utilizaron dos técnicas de radioterapia: la primera durante la década del 90, donde se empleaban dos campos paralelos y opuestos (anterior y posterior) y una segunda actual, donde se irradian en conjunto la pelvis y los lumboaórticos a través de 4 campos (laterales y AP-PA). Resultados: El análisis dosimétrico de las dos técnicas confirma un mayor volumen irradiado de tejidos normales con la técnica de dos campos, fundamentalmente intestino delgado. La toxicidad fue significativamente diferente, siendo la que utilizamos hoy menos tóxica y con bajas complicaciones gastrointestinales, a pesar de recibir un tratamiento de radio-quimioterapia concomitante (55 por ciento vs 0 por ciento). Conclusión: La radioterapia lumboaórtica es un tratamiento con una tolerancia aceptable incluso con quimioterapia concomitante. Esta revisión nos obliga a elaborar un nuevo trabajo para evaluar si la radioterapia lumboaórtica reduce el riesgo de recidiva y aumenta la sobrevida.

Background: Uterine cancer is still a prevalent disease in Chile. Is common to treat patients with tumors in stages IIB and IIIB where the risk of pelvic and paraortic limph node involvement is very high. Its treatment is radio-chemotherapy. Objective: To present a retrospective analysis of patients that suffered cervix-uterine cancer who were treated with radiotherapy including the aortic-lumbar area. Methods: From the revision of patients who were treated of cervix-uterine cancer between the years 1995 and 2007, 39 were treated including aortic-lumbar chains. Evolution and toxicity were analyzed. Two radiotherapy techniques were used. The first one, during the nineties, included two parallel previous and later and opposed fields, and a second technique, currently used, where pelvis and paraortic are radiated at the same time through four lateral (AP-PA) fields. Results: The dosimeter analysis of both techniques shows that there is a higher volume of radiated normal tissue with the two fields techniques, mainly in the small bowel. On the other hand, the toxicity was significantly different being today's technique less toxic and showing low gastrointestinal side effects, despite receiving a simultaneous radio-chemotherapy (55 percent vs 0 percent). Conclusion: The paraortic radiotherapy treatment has an acceptable level of tolerance even under simultaneous radio-chemotherapy. Given the results of this study, we see the need for undergoing a new research project in order to evaluate if the aortic-lumbar radiotherapy may reduce the risk of relapse and increase in survival rate.

Irradiación lumboaórtica en el cáncer cérvico uterino: análisis de la literatura / Radiotherapy of aortic-lumbar lymph nodes in the cervical cancer: literature review

Antecedentes: El cáncer de cuello uterino es una enfermedad prevalente en Chile y es una de las localizaciones tumorales más frecuentes tratadas en el Instituto Nacional del Cáncer. Es habitual recibir pacientes jóvenes con tumores avanzados, en etapas IIB y IIIB, con riesgo elevado de compromiso ganglionar, tanto pelviano como lumboaórtico y donde el tratamiento estándar es la radio-quimioterapia. Objetivos: Determinar si la irradiación lumboaórtica reduce el riesgo de recidiva y/o mejora la sobrevida en pacientes con compromiso ganglionar evidente y en aquellos con alto riesgo de compromiso a dicho nivel. Método: Revisión exhaustiva de la literatura publicada sobre la indicación de radioterapia lumboaórtica en el cáncer cérvico uterino, en pacientes con enfermedad evidente en los ganglios lumboaórticos y en aquellas en que la indicación es en casos de alto riesgo de compromiso en dicho nivel. Resultados: En pacientes con tumores cervicales de pequeño tamaño y con ganglios pelvianos positivos, sería beneficioso el tratamiento ganglionar lumboaórtico. Sin embargo, en aquellas pacientes con enfermedad pelviana masiva (IIIB)o en aquellas en que existe evidencia de enfermedad lumboaórtica, dicho beneficio no sería tan importante. Conclusión: Son las pacientes con enfermedad pelviana controlable y con elevado riesgo de tener compromiso ganglionar lumboaórtico (etapa IA-B, IIA-B con ganglios positivos en la pelvis), las que más se benefician de la radioterapia lumboaórtica.

Background: Uterine cancer is a prevalent disease in Chile and it is one of the most frequent cancer locations treated in the National Chilean Cancer Institute. It is also common to receive young patients that have advanced tumors in stages IIB and IIIB with high risks of compromises of lymphatic nodes of pelvis and aortic-lumbar zones. The treatment for these kinds of cancers is radio-chemotherapy. Aims: Determinate if the radiotherapy of aortic-lumbar lymph nodes lowers the chance of relapsing or increase the survival rate in patients with evident compromise of aortic-lumbar lymph nodes and in those with high risk of compromise in that level. Method: Exhaustive analysis of the literature about the indication of radiotherapy of aortic-lumbar lymph nodes in cervix cancer which is classified in those where the radiotherapy treatment is done in patients with evident compromise of aortic-lumbar lymph-nodes, and those where de radiotherapy is done in patients with high risk of compromise in that level. Results: In patients with small cervix tumors and positive lymphoid nodes the LA lymphatic nodes treatment would be beneficial. However, patients that suffer massive pelvic disease (IIIB) or that have evidence of the disease, the benefit would not be so important. Conclusion: Patients with controllable pelvic disease and with high risk of having aortic-lumbar lymph nodes compromise are the most benefit of radiotherapy in aortic-lumbar lymph nodes (stages IA-B, IIA-B with positive lymph nodes).