Neoadjuvant letrozole and palbociclib in patients with HR-positive/HER2-negative early breast cancer and Oncotype DX Recurrence Score ≥18: DxCARTES study.

BACKGROUND: The effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18. PATIENTS AND METHODS: Participants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR). RESULTS: A total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P = 0.98). No new safety signals were identified. CONCLUSIONS: The efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.

Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2-positive ABC patients with stable or active brain metastases (BMs); however, its efficacy in patients with HER2-low ABC with BMs is not well established yet. METHODS: DEBBRAH is a single-arm, five-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n = 6, asymptomatic untreated BMs) and 4 (n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. RESULTS: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. CONCLUSIONS: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.

Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer.

Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results: A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions: Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation. ClinicalTrials.gov: NCT01091168.

Targeting FGFR pathway in breast cancer.

Developments in breast cancer biology over the last years have permitted deconstructing the molecular profile of the most relevant breast cancer subtypes. This has led to an increase in therapeutic options, including more effective personalized therapy for breast cancer and substantial improvements in patient outcomes. Although currently there are only a few targeted therapies approved for metastatic breast cancer, the discovery of druggable kinase gene alterations has radically changed cancer treatment by providing novel and successfully actionable drug targets. Fibroblast growth factors and their receptors (FGFRs) participate in different physiologic processes and also play an essential role in cancer cell proliferation, survival, differentiation, migration, and apoptosis. This article summarizes the main molecular alterations of FGFRs, as well as the available preclinical and clinical data with FGFR inhibitors in breast cancer, and discusses new opportunities for the clinical development of these agents in patients with breast cancer.

Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors.

The fibroblast growth factor receptor (FGFR) cascade plays crucial roles in tumor cell proliferation, angiogenesis, migration and survival. Accumulating evidence suggests that in some tumor types, FGFRs are bona fide oncogenes to which cancer cells are addicted. Because FGFR inhibition can reduce proliferation and induce cell death in a variety of in vitro and in vivo tumor models harboring FGFR aberrations, a growing number of research groups have selected FGFRs as targets for anticancer drug development. Multikinase FGFR/vascular endothelial growth factor receptor (VEGFR) inhibitors have shown promising activity in breast cancer patients with FGFR1 and/or FGF3 amplification. Early clinical trials with selective FGFR inhibitors, which may overcome the toxicity constraints raised by multitarget kinase inhibition, are recruiting patients with known FGFR(1-4) status based on genomic screens. Preliminary signs of antitumor activity have been demonstrated in some tumor types, including squamous cell lung carcinomas. Rational combination of targeted therapies is expected to further increase the efficacy of selective FGFR inhibitors. Herein, we discuss unsolved questions in the clinical development of these agents and suggest guidelines for management of hyperphosphatemia, a class-specific mechanism-based toxicity. In addition, we propose standardized definitions for FGFR1 and FGFR2 gene amplification based on in situ hybridization methods. Extended access to next-generation sequencing platforms will facilitate the identification of diseases in which somatic FGFR(1-4) mutations, amplifications and fusions are potentially driving cancer cell viability, further strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors.

Thumb metacarpophalangeal joint ligament reconstruction with a triangular tendon graft in posttraumatic chronic instability.

UNLABELLED: The purpose of this study was to report the results of static triangular ligament reconstruction, in thumb metacarpophalangeal (MCP) joint chronic posttraumatic laxity using a tendon graft with a proximal apex in ten patients. The mean postoperative follow-up was 40.2 months. The mean postoperative thumb MCP joint stress testing was 43° less than before surgery, and 6.5° less than in the non-injured hand. The mean range of flexion was 10.5° lower in the operated thumb than in the contralateral one, and the mean range of extension was 8° lower. Minimal differences in the values of the Kapandji score, grip and key-pinch strength were found. The preoperative pain became an occasional discomfort after surgery. All patients had a subjective sense of stability until final follow-up. All patients returned to their work or daily activities. LEVEL OF EVIDENCE IV: For therapeutic studies investigating the results of treatment.

Use of fully covered self-expanding metal stents for the management of benign biliary conditions.

BACKGROUND AND AIM: biliary self-expanding metal stents (SEMS) have the advantage of being inserted undeployed with very small sizes and provide, when fully opened, large diameters for biliary drainage. However, their use in benign conditions has been very limited, mainly because of difficulty in their extraction. We present our initial experience with a fully covered SEMS (Wallflex) for the management of benign problems of the bile duct. PATIENTS AND METHODS: in a prospective study, stents of 8 mm in diameter and 4, 6 or 8 cm long were inserted by means of ERCP. These SEMS were chosen when according to medical judgement it was thought that diameters greater than 10 French (3.3 mm) were needed for proper biliary drainage. Stents were extracted also endoscopically, several months later when deemed clinically appropriate. RESULTS: twenty biliary SEMS were inserted. Reasons for insertion were: large intrahepatic biliary fistula after hydatid cyst surgery (1), perforation of the papillary area following endoscopic sphincterotomy (2), coaxial insertion to achieve patency in obstructed uncovered stents inserted in benign conditions (3), benign strictures (7), multiple and large common bile duct stones that could not be extracted because of tapering and stricturing of the distal common bile duct (7). In all cases, successful biliary drainage was achieved and there were no complications from insertion. Stents were easily extracted after a mean time of 132 days (36-270) in place. Complete resolution of biliary problems was obtained in 14 patients (70%). CONCLUSIONS: in our initial experience, the fully covered Wallflex biliary stent was removed without any complication after being in place in the common bile duct for a mean time of over four months. Therefore, it could be used in the management of benign biliary conditions.

Status of PI3K inhibition and biomarker development in cancer therapeutics.

The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival. The 'phosphate and tensin homologue deleted from chromosome 10' (PTEN) tumor suppressor gene plays a critical role as a negative regulator of this pathway. An array of genetic mutations and amplifications has been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to some classic cytotoxics and targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex machinations and interactions. This knowledge has enabled the evolution of rationally designed drugs targeting elements of this pathway. It is important that the development of suitable biomarkers continues in parallel to optimize use of these agents. A new generation of PI3K inhibitors is now entering early clinical trials, with much anticipation that they will add to the growing armamentarium of targeted cancer therapeutics.

[Palliative management of malignant gastric outlet obstruction with endoscopically inserted self-expanding metal stents].

AIM AND BACKGROUND: the insertion of self-expanding metal stents to palliate malignant gastric outlet obstruction is a minimally invasive procedure that is being increasingly used. We discuss experience with this technique in a level-II hospital in the Spanish National Health System. PATIENTS AND METHODS: a retrospective five-year study (2003-2007) was conducted in 23 patients who underwent 27 procedures aimed at resolving malignant gastric outlet obstruction (mean, 0.45 procedures per month) using endoscopically inserted noncovered stents (Wallstent and Wallflex). RESULTS: insertion was technically feasible in all 27 (100%) attempts, with satisfactory clinical results in 25 cases (92.5%). Endoscopy alone was used 10 times (37%), and both endoscopy and fluoroscopy on 17 (63%) occasions. After stent insertion, one patient was intervened for treatment, and a patient with an unsuccessful prosthesis received a palliative surgical bypass. Four stents became obstructed by tumoral ingrowth, and patency was reestablished by inserting a new stent. Obstructive jaundice caused by stents covering the papilla of Vater occurred in three cases. There were no other complications or mortality due to the procedure. Mean survival was 104 days (range 28-400, SD +/- 94). CONCLUSIONS: in our experience endoscopic insertion of self-expanding metal stents appears to be a safe and efficient palliative method for malignant gastric outlet obstruction, and can be performed successfully in a center with our characteristics.

Outcomes of bile duct drainage by means of ERCP in geriatric patients / Resultados del drenaje de la vía biliar por CPRE en pacientes con edad geriátrica.

BACKGROUND AND OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) is usually the procedure of choice for relieving bile duct obstruction. a large number of patients undergoing this intervention are geriatric population (aged 75 years of age and older). Our aim was to assess the efficacy of ERCP in this group of patients as compared to younger ones. PATIENTS AND METHODS: A retrospective study. All patients in whom a therapeutic biliary endoscopy had been performed over a four-year period of time (2002-2005) were included. RESULTS: 178 geriatric patients and 159 younger ones underwent ERCP. No differences were found in successful biliary drainage (97.7 vs. 98.7%), complication number (11.8 vs. 14.4%), or mortality rate (1.1 vs. 0.6%). On the other hand, more common bile duct stones were found in geriatric patients (57.3 vs. 39.6%, p = 0.004), and also more self-expanding metal stents were employed to drain malignant obstructive jaundice (47 vs. 8%, p = 0.0035). In the youngest group, more ERCPs were repeated in the same patients (4 vs. 10%, p = 0.001). CONCLUSIONS: The geriatric population showed similar success and morbidity and mortality rates when compared to younger patients in draining their bile duct by means of ERCP. Common bile duct stones were more frequently found in geriatric patients. No patients needing an ERCP should be excluded only because of their age.

[Pancreatobiliary maljunction. Not only an Eastern disease]. / Unión biliopancreática anómala. Una enfermedad no exclusiva de pacientes orientales.

Pancreatobiliary maljunction, an extramural junction of the pancreatic and biliary ducts in the duodenum, apparently beyond the scope of intramural sphincter function, is thought to be a preferential disease of Eastern people. However, this diagnosis is increasingly being made in other populations. We present a 41-year-old woman who presented with intermittent epigastric pain and mild raise in amylase levels. MRCP did not offer a definitive diagnosis, perhaps because of lack of experience in this disease. Finally, ERCP showed a pancreatobiliary maljunction, type acute angle, but with a complex connection between the choledocus and the pancreatic duct. Fusiform dilation of the common bile duct and of the left main hepatic duct were also present. The patient was referred for extrahepatic biliary resection and a diversion procedure. But also because of lack of experience in this disease, a wait-and-see approach was undertaken. In conclusion, pancreatobiliary maljunction will be increasingly diagnosed in western communities and more diagnostic and therapeutic experience will be needed.

[Treatment of malignant colorectal obstruction by means of endoscopic insertion of self-expandable metallic stents]. / Tratamiento de la obstrucción neoplástica del colon meciante la inserción endoscópica de prótesis metálicas autoexpandibles.

BACKGROUND AND AIM: Self-expandable metallic stents are being used increasingly to treat the obstruction of different segments of the digestive tract and biliary tree. We present our centre experience on the initial resolution of malignant colorectal obstruction by means of this type of stents. PATIENTS AND METHODS: During a 18-month period, 13 patients patients suffering from malignant obstruction at the level of rectum, sigmoid or descending colon tried to be initially treated by means of endoscopic insertion of stents (non covered enteral Wallstents). Ten procedures were performed with both endoscopy and fluroscopy and three with only endoscopy. RESULTS: In 12 of the 13 patients (92,3%) the obstruction was solved by means of correct stent insertion. All the exclusively endoscopic procedures (without fluoroscopy) were successful. Six (50 %) patients with tumours at the rectosigmoid underwent later scheduled surgery. In the remaining six ones (a patient with an ovarian carcinoma and five with colonic adenocarcinoma) the stents were considered to be a palliative definitive treatment. Stent migration was observed in two of these patients and both were extracted endoscopically. Only one patient needed to have another stent inserted. A tumoural colo-vesical fistula developed in another patient in the palliative group, inside the previous inserted stent, and was treated by coaxial insertion of an esophageal Ultraflex. There were no other complications or mortality related to the endoscopic procedures. CONCLUSIONS: Self-expandable metallic stents might be considered, in general, as the initial treatment for the malignant obstruction at the level of rectum, sigmoid and descending colon

[Locoregional treatment of carcinoma epidermoid of the maxillary sinus]. / Tratamiento locorregional del carcinoma epidermoide de seno maxilar.

Squamous-cell carcinoma of the maxillary sinus is an infrequent neoplasm of poor prognosis. Symptoms are evident when the disease is in an advanced stage. Lymph-node metastases are relatively infrequent. The survival rate of patients with this tumor has improved slightly since Obgren reported his experience in 1933, thanks to oncological and surgical advances since then. We report our experience with 28 surgically treated cases of maxillary-sinus squamous-cell carcinoma in the last 10 years, analyzing the reconstructive procedures applied, the disease-free survival rate, and our treatment protocol. A bibliographic review was made to examine all current therapeutic possibilities.

[Significance of random biopsies of healthy mucosa in superficial bladder tumor]. / Significado de las biopsias al azar de mucosa sana en el tumor de vejiga superficial.

OBJECTIVE: To analyze the characteristics of the random biopsies of normal-appearing mucosa taken during TUR of superficial bladder tumors and to correlate them with the outcome and characteristics of the superficial tumor. METHODS: Multiple random biopsy specimens from normal-appearing areas of 300 TUR procedures for primary or recurrent superficial urothelial carcinoma were analyzed. Preoperative cytologies were obtained in most of the patients and tumor number, localization, size, stage and grade according to the WHO classification were determined. In patients with multiple tumors, the stage, size and grade of the worst tumor were utilized. Patients who showed a risk of recurrence during follow-up received intravesical therapy postTUR of the bladder. The site and characteristics of recurrence were analyzed and compared with the random biopsy findings. RESULTS: In 38 superficial tumors (12.7%), significant histological changes were found in the random biopsies of normal-appearing mucosa taken during resection. A significant difference was found between patients with and without positive random biopsies only for tumor stage. Statistically significant differences were found when comparing the primary and recurrent tumors, due to the greater number of high and moderate grade tumors in the primaries. There were significant differences in regard to the positive preoperative cytologies between the patients with negative and those with positive random biopsies. No statistical correlation was found between the localization of the superficial tumor and a positive biopsy or between the latter and the site of tumor recurrence. There were 126 recurrences (42%); mean time to recurrence was 13.5 months (median 9.5 months). No significant difference was found (log-rank) for time to recurrence in patients with positive or negative random biopsies, but significant differences were found when we analyzed the number of superficial tumors and the use of intravesical therapy, but not for the type of therapy. CONCLUSIONS: Multiple random biopsies permit a better categorization of the tumor and complete staging. The outcome and the decision to administer intravesical therapy following TUR of the bladder are influenced by the foregoing. The practical results of random biopsies, however, are scanty, since the prognostic significance of the histological changes found in these biopsies is not worse than that of the superficial tumor resected. There are, however, a few cases with a higher risk of recurrence and/or progression than the superficial tumor. Preoperative cytology is useful in the selection of these patients. Furthermore, since the proportion of high grade tumors is higher in primary tumors, performing multiple biopsies is mandatory in these cases if previous urine cytology is not available.

[Risk of tumor seeding after nephroureterectomy combined with endoscopic resection of the ureteral meatus]. / Riesgo de implantación tumoral tras la nefroureterectomía combinada con resección endoscópica del meato ureteral.

OBJECTIVE: To describe a case of tumor implantation at the site of resection in the ureteral orifice, following nephroureterectomy combined with resection of the bladder cuff of. METHODS/RESULTS: A patient with high grade and stage carcinoma of the renal pelvis and no previous bladder tumor presented with a perivesical mass 6 months following nephroureterectomy. She had a high grade transitional cell carcinoma that infiltrated all of the bladder wall, vagina and parametrium in the region of the meatus that had been resected endoscopically. CONCLUSIONS: The present case indicates there may be histological or technique-related factors that facilitate tumor cell implantation in the deep perivesical region after this procedure is performed. It is necessary to identify these factors before this procedure is used widely.

[Interventricular communication in the neonatal period]. / Comunicación interventricular en la edad neonatal.

OBJECTIVE: The aim of this study was to evaluate the prevalence and the follow-up in the long run of ventricular septal defect in the neonatal period. MATERIAL AND METHODS: 222 patients with ventricular septal defect from a total amount of 30,840 newborns admitted to our Hospital were evaluated between January 1991 and December 1996 (The incidence accounts for 7.19 per 1,000 newborns). 123 of these patients were males (55.4%) and 99 females (44.6%). The mean age at the time of examination was 3.09 +/- 1.67 days (range from 1 to 11 days). Diagnosis was suspected because of a harsh systolic murmur in 207 cases (93.2%), a malformative syndrome in 10 (4.5%) or polypnea in 5 (2.3%). The study was performed with a Sonos 1000 Echocardiograph device. The mean follow-up period ranged from 1 to 72 months. 10 patients underwent cardiac catheterization (4.5%). RESULTS: A muscular defect was the common finding in 177 patients (79.7%) whereas 41 patients (18.5%) exhibited a perimembranous defect. The mean size defect was 2.9 +/- 1.2 mm (range 1-10 mm), being smaller in the muscular defects (2.56 +/- 0.68) than in the perimembranous defects (4.33 +/- 1.56) p < 0.001. Spontaneous closure occurred in 176 ventricular septal defects (79.3%), 155 of them corresponding to muscular defects (87.6%) and 18 to perimembranous defects (43.9%). The mean age at the time of spontaneous closure was 9.5 +/- 8.9 months (9.4 +/- 9 months in the muscular defects and 10.3 +/- 4 months in the perimembranous defects). Spontaneous closure occurred by age 6 months in 52% of the patients with ventricular septal defect (54.5% muscular defects, 33.3% perimembranous defects), 12 months in 72.7% (71.2% muscular defects and 83.3% perimembranous defects) and 24 months in 96% (96.1% muscular defects and 94.4% perimembranous defects). 10 patients underwent surgical repair by age 11 +/- 8 months. All of them exhibited perimembranous defects with a mean size 6 +/- 1.5 mm which were tantamount to 24.4% of this group. 3 patients died (1.4%), 2 suffering from trisomy 18 and 1 after cardiac surgical repair. CONCLUSION: The most common ventricular septal defects in the neonatal period occur in the region of the muscular septum. The prognosis is favourable. Most of the patients experience spontaneous closure and show a very low mortality rate which is basically related to extracardiac anomalies.

[Frequency and current clinical diversity of cerebral cortical dysgenesis]. / Frecuencia y diversidad clínica actual de las disgenesias corticales cerebrales.

OBJECTIVE: The extended use of MRI has increased the number of patients diagnosed of cortical dysgenesis and has changed the clinical spectrum usually associated with this disorder. The aim of this study was to know the frequency and clinical variety of cortical dysgenesis in our current patient population. PATIENTS AND METHODS: All patients with dysgenesis of the neocortex or of the hippocampus, according to radiological or pathological features, were selected from the total number of patients attended during 1996 at an outpatient hospital-based neuropediatric clinic. Malformations of cerebellar cortex and neurocutaneous syndrome were excluded. RESULTS: Twenty-one patients (1.3% of all patients attended at the clinic) studied by MRI showed polymicrogyria (43%) which was of perisilvian localization in three patients, heterotopias (33%), dysplasia of the hippocampus (24%), agyria-pachygria (14%) and hemimegaencephalia (5%). Three patients underwent surgical interventions. Epilepsy was present in 90%, mental retardation in 68%, cerebral palsy 47%, infantile spasms 40%, microcephally 25%, autism 10%, hyperkinesis 5% and learning disabilities in 33% of those school age children free of mental retardation. CONCLUSIONS: The actual prevalence of cortical dysgenesis at our clinic is similar to that of neurodevelopmental impairments following birth-asphyxia (1.2%), amounting to two thirds of those following prematurity and to half of those following a brain injury of late prenatal onset. Except for the almost constant presence of epilepsy, especially infantile spasms, clinical symptomatology is diverse and occurs in a similar percentages in brain lesions acquired during labour or during late pregnancy. Hyperkinesis and autism have a similar prevalence to that seen in the total number of patients attended at the clinic during 1996.