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.

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.

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.

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 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.

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.

Braquiterapia endobronquial de alta tasa de dosis en pacientes con obstrucción de la vía aérea central: experiencia en el Instituto Nacional del Cáncer y revisión de la literatura / High dose rate endobronchial brachytherapy in patients with central airway obstruction

Introduction: The main indication of modern high dose rate end bronchial brachyherapy (HDR EBBT) is the palliation of symptoms related to the growth of the endobronchial lung cancer. Methods: EBBT was performed to 27 patients who suffered symptomatic tumoral endobronchial or tracheal pathology, due to primary bronchial disease or secondary metastasis cancer, evaluating the rate of clinical benefit. The tumors were located at tracheal, carinal or proximal bronchial level. Fibrobronchoscopy was performed to all the patients to measure the degree of airway obstruction and to install brachytherapy endobronchial catheters. Between 1 to 4 fractions of 7 to 7.5 Gy were administered. Dyspnea, cough and hemoptysis were subjectively registered before and after treatment, according to an international validated scale. Results: After treatment, all symptoms considerably decreased, disappearing all of the severe categories. Hemoptysis and dyspnea resolved in a 100 percent and 40 percent of patients, respectively; and cough disappeared or was reduced to a minimum grade in 90 percent of cases.

Introducción: La indicación principal de la braquiterapia endobronquial moderna (BTEB) de alta tasa de dosis (HDR), es la paliación de síntomas por crecimiento endobronquial de cánceres pulmonares. Métodos: Se realizó BTEB HDR a 27 pacientes sintomáticos de patología tumoral endobronquial o traqueal, debido a patologías primarias bronquiales o secundarias metastásicas. Los tumores se ubicaban en tráquea, carina o a nivel bronquialproximal. Para observar mejorías en la sintomatología clínica, a todos se les realizó una fibrobroncoscopía (FBC) para medir el grado de obstrucción bronquial e instalar catéteres endobronquiales de braquiterapia. Se administraron entre 1 y 4 fracciones de 7 a 7,5 Gy. Se registró subjetivamente la disnea, tos y hemoptisis antes y después del tratamiento, de acuerdo a una escala internacionalmente validada. Resultados: Tras el tratamiento todos los síntomas disminuyeron considerablemente, desapareciendo toda sintomatología severa. La hemoptisis y disnea desaparecieron en el 100 por ciento y 40 por ciento de los pacientes respectivamente, y la tos desapareció o disminuyó a grado leve en el 90 por ciento de los pacientes.

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).

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.

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.

Diagnostic accuracy of fecal elastase 1 assay in patients with pancreatic maldigestion or intestinal malabsorption: a collaborative study of the Italian Society of Pediatric Gastroenterology and Hepatology.

Several reports have indicated that fecal elastase-1 (EL-1) determination is a new, sensitive, and specific noninvasive pancreatic function test; however, very few patients with malabsorption due to small intestine diseases have been included in the previous studies. The aim of the study was to compare the diagnostic accuracy of fecal EL-1 and fecal chymotrypsin (FCT) in distinguishing between pancreatic maldigestion and intestinal malabsorption. Three groups of subjects were studied: group A included 49 patients with known cystic fibrosis (25 males, median age 5 years); group B included 43 subjects with various small intestine diseases (17 males, median age 6 years); and group C included 45 children without any history of gastrointestinal disease (22 males, median age 5 years). In all patients, stools were collected for 72 h on a standard diet and fecal EL-1, FCT, and steatocrit tests were performed. Both EL-1 and FCT were below normal limits in all CF patients with pancreatic maldigestion not treated with pancreatic enzyme (100% sensitivity for both assays); El-1, but not FCT, was also below normal in all the CF patients with pancreatic maldigestion treated with pancreatic extracts. Both EL-1 and FCT values in the CF group were significantly lower than in subjects with various small intestinal diseases and in children without any history of gastrointestinal disease (P < 0.0001). FCT, but not EL-1, values showed an inverse statistically significant correlation with steatocrit values in the whole CF group (P < 0.001); FCT was below normal in three of four CF patients with steatorrhea on pancreatic enzyme therapy. Both EL-1 and FCT had 100% specificity when calculated in children without any history of gastrointestinal disease; in contrast, specificity was 86% for EL-1 and 76% for FCT if we considered the control group with small intestinal diseases: low EL-1 was observed in two cases of intestinal giardiasis, two cases of short bowel syndrome, one case of celiac disease, and one case of intestinal pseudobstruction; FCT was abnormal in four cases of intestinal giardiasis, three cases of celiac disease, one case of short bowel syndrome, one case of Crohn's disease, and one case of intestinal pseudobstruction. Diagnostic accuracy was 92% for fecal EL-1 and 82% for FCT. Steatocrit values were over the normal limit in 11 patients with small intestine diseases; in 7/11 of these patients at least one of the pancreatic test results was below the normal limit. In conclusions, in patients with CF, fecal EL-1 determination is not more sensitive than FCT in identifying pancreatic maldigestion; however, fecal EL-1 assay is more specific than FCT determination in distinguishing pancreatic maldigestion from intestinal malabsorption.

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.

[Adolescence in patients with cystic fibrosis studied by Rorschach test]. / L'adolescenza nei pazienti con fibrosi cistica studiata col test di Rorschach.

BACKGROUND: The majority of patients with cystic fibrosis today reach adulthood. During adolescence, however, many ask themselves questions regarding their possible future realisation. AIMS: The aim of this study, which was performed using the Rorschach test, was to identify areas of particular problems in a group of CF adolescents monitored by the Pneumology Division of Regina Margherita Children's Hospital in Turin: 26 subjects aged between 14 and 18, including 11 females and 15 males. METHODS: The analysis of the test was based on the use of thought, interior resources, instincts and interpersonal relations. The type of intimate resonance was also taken into account and, lastly, a study of the contents was performed using a self-representation grid. RESULTS: The results obtained show a dishomogeneous profile of the development and quality of intellectual processes faced with the intensity of anxiety, mainly loss anxiety, linked to the disease, even if unrelated to its severity. The integration of emotive and instinctual aspects is difficult: mental development towards adult life appears to be impeded by the predominance of regressive modalities. CONCLUSIONS: On the basis of the study performed, it is possible to hypothesise the need for psychological help aimed at achieving a more evolved psychic organisation, possible as part of an overall management programme by the medical and nursing team.

[Personality structure in children with cystic fibrosis studied using Rorschach test]. / La strutturazione della personalità nei bambini con fibrosi cistica studiata col test di Rorschach.

BACKGROUND AND AIMS: The recent positive evolution in the development of cystic fibrosis, resulting in the current prospect of survival, has led to the formation of a new population of chronic patients. The characteristics of the disease and treatment (hereditary, early onset, affecting the alimentary tract and airways) may interfere with personality structuring processes. The aim of the study was to identify the psychopathological risk. METHODS: The study was performed using the Rorschach test in a population of children with cystic fibrosis monitored by the Pneumology Division of the Ospedale Infantile Regina Margherita in Turin: 20 children aged between 7 and 13 years old were included in the study, most of whom had been diagnosed before the age of 2. The analysis of tests was focused on the use of thought, interior resources, instincts and interpersonal relations. A study of the contents was also made using a self-representational grid. RESULTS: The results obtained highlight an inhibitory attitude which cannot be attributed to intellectual insufficiency, but rather to the failed attempt to invest in the intellectual sphere, typical of this age range, owing to the intensity of anguish. Children with cystic fibrosis appear to be at an earlier stage of development, marked by emotive coarctation and the use of adult-type defensive methods, tending towards rationalisation. CONCLUSIONS: Oh the basis of this study, it is possible to detect a danger of disharmonious organisation in the personality structuring process of these children. The hospital must therefore offer adequate psychological support for their psychic evolution.

[Home enteral nutrition in pediatric age. Based on the Torino experience]. / La nutrizione enterale domiciliare (NED) in età pediatrica. Esperienza del polo di riferimento di Torino.

Enteral nutrition is increasingly used in the management of sick children. Malnutrition may frequently complicate chronic illness in children and nutritional support may be a primary treatment. Particularly children with malnutrition due to certain chronic disorders may need long term enteral nutrition not only in hospital but also at home. We report our experience on home enteral nutrition of 14 patients, aged from 3 months to 15 years. Eleven had a serious weight deficit (< 3 degrees percentile), but none had severe alteration of the biohumoral nutritional parameters. The indication for EN were: in 7 patients cerebral palsy, in 2 cystic fibrosis, and in the other 5 patients congenital heart disease, multiple food intolerance, oesophageal athresia, Werding-Hoffman disease, Costello's Syndrome. Nutritional support was given by nasogastric tube in 6 patients, through gastrostomy in 3 patients and by mouth in 5 patients. We did not see any severe complication due to home enteral nutrition. The practicalities of this nutritional approach are discussed. Although home enteral nutrition was evaluated in a low number of patients, it may have a role in promoting growth of children with inadequate dietary intake or malnutrition and in improving their quality of life.

[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.

[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.