LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Interstitial iridium-192 for bladder cancer (a multicentric survey: 205 patients).

Interstitial irradiation is a technique currently used in the treatment of bladder cancer. We report the data on 205 patients (177 men and 28 women) treated in eight French centers. The patients had received the following treatment: a short course of pre-operative pelvic irradiation, followed by surgery consisting of partial cystectomy or tumor resection, and implantation of plastic tubes filled with inactive lead wires, which were replaced by iridium 192 wires. The tumor characteristics were: transitional cell carcinoma, 88.8%; mean size of the tumor, 29 mm; pathological stages: pTis, 1; pT1, 98; pT2, 66; pT3a, 26; pT3b, 9; pT4, 1; unknown, 4 respectively; surgical lymph node status: N+, 3; N-, 118; no node dissection, 84. The mean follow-up was 51 months. Intravesical failures were seen in 35 patients (17.0%), 25 (71.4%) of them without metastases or regional recurrences. Twenty-one patients (10.2%) presented distant metastases, 2/3 of them suffered no bladder relapse. The 5-year survival, calculated according to the Kaplan-Meier method (all causes of death taken together) was 77.4% for the T1, 62.9% for the T2, and 46.8% for the T3. Fifty-three patients had immediate side-effects and three died from surgical complications. Twenty-nine patients had delayed bladder side-effects (haematuria, fistula, chronic cystitis). Six patients presented an ureteral stenosis. Of the disease-free survivors, 96.1% retained the bladder function. Three factors were significantly predictive of delayed side-effects: partial cystectomy, pre-operative radiotherapy total dose, and linear activity of the wires (p < 0.01). Comparing our results to different authors' series interstitial irradiation is likely to provide a high local and general control of the disease and good quality of life in patients with selected tumors.     

Comparative study and clinical implementation of two breathing-adapted radiotherapy techniques: dosimetric benefits for lung cancer treatment]

Breathing can lead to organ motions up to several centimeters. For radiotherapy of lung, these motions are generally taken into account by adding a specific margin around the target. Thus, treated volumes are often too large to allow for the high-dose values requested for local control. To manage respiratory motion, deep-inspiration breath-hold technique (DIBH) and gated radiotherapy are starting being used clinically. DIBH consists in asking the patient to perform breath-hold during the treatment and the image acquisition, DIBH level being measured by a spirometer. Gated radiotherapy consists in treating the patient at a certain phase of the free breathing. Linac is synchronized with the motion of a marker located on the patient chest. Planning images are obtained by a four-dimensional CT (4D-CT) using the same marker. We have assessed the value of these two methods. For lung treatment, compared to a standard treatment, toxicity reduction was mainly due to the lung total volume increase. It is therefore more significant for breath-hold approach. It is also due to the reduction of safety margins, which is similar for both methods. These two techniques, which have specific advantages and drawbacks, are used routinely at Curie Institute for a large proportion of lung patients, but also for some breast, liver or even Hodgkin disease treatments.     

Evaluation of a new enzyme-linked immunosorbent assay test for rotavirus antigen in faeces

A new commercial test for the diagnosis of rotavirus gastroenteritis was assessed. With some modifications it compared favourably with electron microscopy and immunofluorescence.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions

von Hippel-Lindau (VHL) disease arises from mutations in the VHL gene and predisposes patients to develop a variety of tumors in different organs. In the kidney, single or multiple cysts and renal cell carcinomas (RCC) may occur. Both inter- and intrafamilial heterogeneity in clinical expression are well recognized. To identify VHL-dependent genetic factors, we investigated the renal phenotype in 274 individuals from 126 unrelated VHL families in whom 92 different VHL mutations were characterized. The incidence of renal involvement was increased in families with mutations leading to truncated protein (MLTP) or large rearrangement, as compared to families with missense changes (81 vs. 63%, respectively; P=0.03). In the latter group, we identified two mutation cluster regions (MCRs) associated with a high risk of harboring renal lesions: MCR-1 (codons 74-90) and MCR-2 (codons 130-136). In addition, the incidence of RCC was higher in families with MLTP than in families with missense changes (75 vs. 57%; P=0.04). Furthermore, mutations within MCR-1 but not MCR-2 conferred genetic susceptibility to develop RCC. Overall, our data argued for a substantial contribution of the genetic change in the VHL gene to susceptibility to renal phenotype in VHL patients.     

Duchenne type muscular dystrophy and consanguinity: difficulties in pedigree analysis.

We report the case of a 2-year-old girl who had signs of Duchenne type muscular dystrophy on clinical, electromyographic, laboratory, and pathological examination. The parents of the child are first cousins. A brother and nephew of the mother also had Duchenne type muscular dystrophy. Karyotype analysis in the proband showed both X chromosomes to be morphologically normal. The mother had very high plasma CK levels, equivalent to those observed in carriers of the disease. We discuss different hypothetical mechanisms designed to account for the family pedigree.