Expression of beta-catenin in gastroenteropancreatic endocrine tumours: a study of 229 cases

AIMS: To clarify the role of beta-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of beta-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in beta-catenin expression. METHODS: 229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of beta-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of the CTNNB1 gene. RESULTS: The distribution of immunoreactive beta-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of the CTNNB1 gene in any case. The seven cases with nuclear accumulation of beta-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months. CONCLUSIONS: Immunohistochemically detectable nuclear accumulation of beta-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations in CNNTB1 exon 3. Changes in beta-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.     

The American Digestive Health Foundation: Advancing digestive health through support of research and education in the cause, prevention, treatment, and cure of digestive diseases

This article has no abstract. To view the article, select the "View Print Version (PDF)" link above.     

Comparaison de sérum salé, d’air et d’un mélange oxygène–protoxyde d’azote pour le remplissage des ballonnets de sondes d’intubation chez l’enfant ? Étude prospective randomisée

Objective

The purpose of the present study was to compare how many inflate and deflate are necessary to maintain the endotracheal tube cuff pressure between 15 and 35 cm H₂O by using air, O₂–N₂O mix or saline solution.

Study design

Randomized and prospective study.

Patients and methods

Ninety children from 1 month to 15 years of age were included in the study. All patients were ventilated with O₂50%–N₂O50%. Subsequently, the patients were divided in three groups: (1) Group 1: patients with air inflated cuffs; (2) Group 2: patients with O₂–N₂O mix inflated cuffs; (3) Group 3: patients with saline solution inflated cuffs. In all groups cuffs were inflated to reach an intracuff pressure of 20 cmH₂O. The cuff pressure was then monitored every 10 minutes and adjusted to be between 15 and 35 cmH₂O. Laryngeal and tracheal symptoms were noted in the recovery room.

Results

The three groups of patients were similar for age, weight, and sex. The length of surgery was significantly longer in Group 3. The deflate rate was higher in Group 1 (60%) than in Group 2 (10%) or 3 (3.3%) (p < 0.0001). The inflate rate was higher in Group 2 (76.6%) than in Group 1 or 3 (both 3.3%) (p < 0.0001). Side effects were comparable in the three groups of patients.

Conclusion

Using air or O₂–N₂O mix to inflate cuffs is not reliable. SSI helps to maintain a more stable cuff pressure but monitoring is difficult and sometimes contraindicated by tracheal tubes producers. Inflating cuffs with air and regularly monitoring pressure is the most reliable and easiest technique.     

Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502_503dup and KIT exon 11 557_559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.     

Continuous peripheral nerve blocks for postoperative analgesia in children: feasibility and side effects in a cohort study of 339 catheters

Introduction

Perioperative continuous peripheral nerve blocks (CPNB) are increasingly being used in children. Only one previous study has reported adverse events of CPNB in a high number of pediatric cases. We evaluated the indications, block efficacy, and adverse events related to CPNB in children.

Methods

All CPNBs that were performed in children for postoperative analgesia over a 5-year period at the Montpellier University Hospital in France were included in this study. The first bolus dose and the continuous doses of local anesthetic were not standardized. In the postoperative period, demographic data, quality of analgesia, amount of rescue analgesic medication, child/parent satisfaction, and adverse events were recorded in our Departmental Regional Anesthesia registry.

Results

A total of 339 catheters were evaluated in 292 children ASA physical status I to III. The median age was 8 yr (0.6–17 yr) and the median weight was 28 kg (7–116 kg). The main surgical indications were hip, femoral, or tibial osteotomies (44.5%) and club foot repair (27.4%). The local anesthetics used were either bupivacaine or ropivacaine. The mean volume of the local anesthetic bolus dose was 0.49 ± 0.16 mL · kg^?1, and the mean regimen of local anesthetic continuous infusion was 0.11 ± 0.04 mL · kg^?1 · hr^?1. The median duration of CPNB was 61.6 hr (range 0–264 hr). Pain relief, which was evaluated with the children at rest, was considered optimal in the majority of patients throughout the study period. The Children and Infants Postoperative Pain Scale (CHIPPS) was used in children age 0–6 yr and the Visual Analog Pain Scale (VAS) was used in children 7 yr and older. There were no major adverse events. There were 211 minor adverse events recorded in 153 CPNBs (45.1%). The most frequently reported complication (20.1%) involved mechanical problems with the catheter, followed by nausea and vomiting (14.7%).

Conclusion

CPNBs are indicated after orthopedic surgery in children. Our results demonstrate that CPNBs are feasible in the pediatric setting, and in skilled hands, they promote prolonged analgesia in the majority of patients without major adverse events. The most common minor adverse events are catheter-related mechanical problems and postoperative nausea and vomiting.     

Multiple gastro-intestinal stromal tumors (GIST) in a patient with type I neurofibromatosis revealed by chronic bleeding: pre-operative radiological diagnosis

Recent studies have pointed out a high incidence of GIST, usually multiple and of small intestinal location, in patients with type I neurofibromatosis. We here report an additional case, revealed by chronic gastro-intestinal bleeding and diagnosed at pre-operative imaging studies. A 56-year-old patient, with known type I neurofibromatosis, was referred to our department for the exploration of chronic gastro-intestinal bleeding during anti-aggregant therapy. Endoscopical examination was negative. Enteroscanner showed the presence of four tumor lesions, 3 in the jejunum and 1 in the ileum. Segmental surgical resections were performed. At histological examination, 2 of among the 3 jejunal lesions were diagnosed as typical GIST, of low risk of malignancy, CD117+, CD34+, whereas the last jejunal and ileal lesions were identified as fibroid tumors. Mutations of c-kit gene and of the gene coding for PDGF-Ralpha were not detected. Post-operative recovery was uneventful; no recurrent bleeding was observed. Our case report underlines the potential role of enteroscanner in the management of patients with type I neurofibromatosis with possible digestive complications. It also emphasizes the importance of an accurate diagnosis of the digestive tumors associated with type I neurofibromatosis: GISTs are frequent in this setting and must not be misdiagnosed as neurofibromas.