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Biomedical subjects

G Fromont

Publications and source records attributed to G Fromont.

At least 19 recordsLinked to original sources

The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression.

CDKN2A locus on chromosome 9p21 encodes two tumour suppressor proteins pl6INK4A, which is a regulator of the retinoblastoma (RB) protein, and p14ARF, which is involved in the ARF-Mdm2-p53 pathway. The aim of this study was to determine if CDKN2A gene products are implicated in differentiated thyroid carcinogenesis and progression. We used real-time quantitative RT-PCR and immunohistochemistry to assess both transcripts and proteins levels in 60 tumours specimens. Overexpression of p14ARF and pl6INK4A was observed in follicular adenomas, follicular carcinomas and papillary carcinomas, while downregulation was found in oncocytic adenomas compared to nontumoral paired thyroid tissues. These deregulations were statistically significant for pl6INK4a (P=0.006) in follicular adenomas and close to statistical significance for p14ARF in follicular adenomas (P=0.06) and in papillary carcinomas (P=0.05). In all histological types, except papillary carcinomas, we observed a statistically significant relationship between p14ARF and E2F1 (r=0.64 to 1, P<0.05). Our data are consistent with involvement of CDKN2A transcript upregulation in thyroid follicular tumorigenesis as an early event. However, these deregulations do not appear to be correlated to the clinical outcome and they could not be used as potential prognostic markers.

Adenocarcinoma, Follicular↗

S100A6 (Calcyclin) is a prostate basal cell marker absent in prostate cancer and its precursors.

S100A6 (Calcyclin) is a calcium-binding protein that has been implicated in a variety of biological functions as well as tumorigenesis. The aim of our study was to investigate the involvement of S100A6 during prostate cancer development and progression. Using immunohistochemistry, the expression of S100A6 was examined in benign (n=66), premalignant (n=10), malignant (n=66) and metastatic prostate (n=5) tissues arranged in a tissue-microarray or whole sections as well as in prostate cancer cell lines. The S100A6 immunostaining pattern in tissues was compared with that of cytokeratin 5 (a basal cell marker) and 18 (a benign luminal cell marker). In all cases of benign epithelium, intense S100A6 expression was seen in the basal cell layer with absent staining in luminal cells. In all cases of prostatic adenocarcinoma (matched), metastatic lesions and 3/10 high-grade prostatic intraepithelial neoplasia lesions, an absence of S100A6 was seen. Western blotting and RT-PCR analysis of cell lines showed S100A6 expression to be absent in LNCaP, LNCaP-LN3 and LNCaP-Pro5 but present in Du145, PC3, PC-3M and PC-3M-LN4. LNCaP cells treated with 5-Azacytidine, caused re-expression of S100A6 mRNA. Sequencing of bisulphite modified DNA showed CpG methylation within the S100A6 promoter region and exon 1 of LNCaP, LNCaP-LN3 and LNCaP-Pro5 cell lines but not in Du145 cells. Our data suggest that loss of S100A6 protein expression is common in prostate cancer development and may occur at an early stage. The mechanism of loss of expression may involve hypermethylation of CpG sites. The finding of intense S100A6 expression in the basal cells of benign glands but loss of expression in cancer could be useful as a novel diagnostic marker for prostate cancer.

Adenocarcinoma↗

[Pulmonary hyalinising granuloma with mediastinal fibrosis: a rare cause of dysphagia].

Pulmonary hyalinising granulomas (PHG) are rare. They are defined by the presence of collagen lamellar fibrosis. One third are associated with retroperitoneal or mediastinal fibrosis. Two cases of PHG are presented. They were revealed by dysphagia due to tight oesophageal stricture from associated mediastinal fibrosis. PHG are considered as a benign and slowly evolving disease, but associated mediastinal fibrosis may evolve on its own. Only steroid therapy may slow down progression. This makes an accurate diagnosis necessary. It relies on large surgical biopsies.

Adult↗

Initial experience in laparoscopic partial nephrectomy for renal tumor with clamping of renal vessels.

PURPOSE: To describe our initial experience with laparoscopic partial nephrectomy (LPN) with clamping of the renal vessels before tumor excision and suturing of the renal parenchyma. PATIENTS AND METHODS: Between July 2001 and April 2002, 19 consecutive patients underwent transperitoneal LPN in our institution, 14 for tumors <4 cm with suspicion of renal-cell cancer and 5 for suspicion of angiomyolipoma at CT with one tumor confirmed histopathologically by percutaneous needle biopsy. We divided these patients into the first 10 cases (Group 1) and the last 9 cases (Group 2). One patient had end-stage renal disease but was not on dialysis; the remaining patients had elective partial nephrectomy. Initially, a ureteral catheter was placed. The partial nephrectomy was performed with clamping of the renal vessels, so that the tumor was excised with cold scissors. Intracorporeal cooling of the kidney was achieved by a ureteral catheter connected to a 4 degrees C solution flowing to the renal pelvis during the whole procedure until the clamps were released. Intracorporeal free-hand suturing was exclusively used to close the collecting system (when opened) and to approximate the renal parenchyma. RESULTS: All procedures were completed laparoscopically. The mean renal warm ischemia time was 28.5+/-7 minutes (range 15-47 minutes). The mean laparoscopic operating time was 125+/-37 minutes (range 90-390 minutes). The mean intraoperative blood loss was 290+/-276 mL (range 25-1200 mL). Two patients required blood transfusion, and four had complications. There was immediate deterioration in renal function (creatinine 1.42+/-0.56 mg/dL), but improvement was seen at 1 month (1.17+/-0.34 mg/dL). There were no statistically significant differences in operative features and outcomes in Groups 1 and 2, but there were improvements in the mean operating time by 30 minutes, the mean intraoperative blood loss by 113 mL without any transfusion, and the mean renal warm ischemia time by 6 minutes. There was only one patient in Group 2 with a complication. The surgical margin was negative for tumor for all patients. Postoperative pathology examination showed renal-cell cancer in 11 patients (pT1), oncocytoma in 3 patients, and angiomyolipoma in 5 patients. The mean tumor grade was 2. The mean tumor size was 25.8+/-11.6 mm with a mean tumor-free margin of 2.6+/-2.4 mm. The median follow-up is 3 months, so oncologic outcome cannot be assessed. CONCLUSION: The technique of LPN can be standardized and should be proposed for small tumors when they are not invading the hilum. Clamping the renal pedicle allows better vision for more accurate tumor excision with a safety margin and hemostatic suturing of the parenchymal defect, resulting in less blood loss and shorter operative time, parameters that improve with experience.

Adenoma, Oxyphilic↗

Laparoscopic partial nephrectomy for renal tumor: single center experience comparing clamping and no clamping techniques of the renal vasculature.

PURPOSE: We performed a nonrandomized retrospective comparison of 2 techniques for laparoscopic partial nephrectomy, that is without and with clamping the renal vessels. MATERIALS AND METHODS: Between December 1997 and February 2002, 28 consecutive patients underwent transperitoneal laparoscopic partial nephrectomy for renal tumor. In group 1 (12 patients) partial nephrectomy was performed with ultrasonic shears and bipolar cautery without clamping the renal vessels, while in group 2 (16 patients) the renal pedicle was clamped before tumor excision. In group 2 patients intracorporeal kidney cooling was achieved by a ureteral catheter connected to 4C solution. Intracorporeal freehand suturing techniques were used to close the collecting system when opened and approximate the renal parenchyma. RESULTS: All procedures were successfully completed laparoscopically. Mean renal ischemia time +/- SD was 27.3 +/- 7 minutes (range 15 to 47) in group 2 patients. Mean laparoscopic operating time was 179.1 +/- 86 minutes (range 90 to 390) in group 1 compared with 121.5 +/- 37 minutes (range 60 to 210) in group 2 (p = 0.004). Mean intraoperative blood loss was significantly higher in group 1 than in group 2 (708.3 +/- 569 versus 270.3 +/- 281 ml., p = 0.014). Three patients in group 1 and 2 in group 2 required blood transfusions. Immediately postoperatively mean creatinine was 1.26 +/- 0.36 and 1.45 +/- 0.61 mg./dl. in groups 1 and 2, respectively (p = 0.075). Surgical margins were negative in all specimens. Pathological examination revealed renal cell cancer in 18 cases (stages pT1 in 17 and pT3a in 1), oncocytoma in 4, angiomyolipoma in 5 and renal adenoma in 1. CONCLUSIONS: Laparoscopic partial nephrectomy represents a feasible option for patients with small renal masses. Clamping the renal vessels during tumor resection and suturing the kidney mimics the open technique and seems to be associated with less blood loss and shorter laparoscopic operative time.

Aged↗

Laparoscopic radical prostatectomy: oncological evaluation after 1,000 cases a Montsouris Institute.

PURPOSE: We performed a prospective oncological evaluation of laparoscopic radical prostatectomy in regard to local tumor control and biochemical recurrence. MATERIALS AND METHODS: Between January 1998 and March 2002, 1,000 consecutive patients with a mean age +/- SD of 63 +/- 6.2 years and clinically localized prostate cancer underwent laparoscopic radical prostatectomy at 1 institution. Preoperative 1997 TNM clinical stage was T1a in 6 patients (0.6%), T1b in 3 (0.3%), T1c in 660 (66.5%), T2a in 304 (30.4%) and T2b in 27 (2.7%). Mean preoperative prostate specific antigen (PSA) +/- SD was 10 +/- 6.1 ng./ml. (range 1.5 to 55). Postoperatively, surgical specimens were assessed and positive surgical margins recorded. Factors that could influence the surgical margins status were evaluated. Irrespective of pathological stage or surgical margin status, no adjuvant treatment was proposed before an increasing PSA. PSA recurrence was defined as PSA greater than 0.1 ng./ml. and was confirmed by a second increase. Recurrence time was defined as the time of the first increase in PSA. RESULTS: Postoperative pathological stage was pT2aN0/Nx in 203 patients (20.3%), pT2bN0/Nx in 572 (57.2%), pT3aN0/Nx in 142 (14.2%), pT3bN0/Nx in 77 (7.7%) and pT1-3 N1 in 6 (0.6%). Positive surgical margin rate was 6.9%, 18.6%, 30% and 34% for pathological stages pT2a, pT2b, pT3a and pT3b, respectively (p <0.001). The main predictors of a positive surgical margin were preoperative PSA (p <0.001), clinical stage (p = 0.001), pathological stage (p <0.001) and Gleason score (p = 0.003). The overall actuarial biochemical progression-free survival rate was 90.5% at 3 years. According to the pathological stage, the progression-free survival rate was 91.8% for pT2aN0/Nx, 88% for pT2bN0/Nx, 77% for pT3aN0/Nx, 44% for pT3bN0/Nx and 50% for pT1-3N1 (p <0.001). Of the patients 94% with negative surgical margins and 80% with positive margins had progression-free survival (p <0.001). Preservation of the neurovascular bundles in patients with localized tumors had no significant effect on the subsequent risk of positive surgical margins or progression-free survival. CONCLUSIONS: Based on followup, our evaluation confirms that laparoscopic radical prostatectomy provides satisfactory results in regard to local tumor control and biochemical recurrence.

Actuarial Analysis↗

Achalasia: the case for primary laparoscopic treatment.

Laparoscopic Heller myotomy offers the best-known surgical therapy for esophageal achalasia. Nevertheless, this procedure continues to compete with alternative endoscopic treatment and is often considered only as a secondary resort. In this study, the authors performed a review of the results of laparoscopic Heller myotomy and an evaluation of the impact of previous endoscopic treatment regarding perioperative complications and late results. Twenty-seven patients with achalasia confirmed by a manometry examination underwent a primary laparoscopic Heller myotomy (group 1, n = 14) or experienced endoscopic treatment failure (group 2, n = 13). A dysphagia score (0-4) was obtained before and after surgery. Clinical course was reviewed at 2 months and then every 6 months after surgery. In December 1999, patients answered a questionnaire regarding surgery satisfaction, postoperative reflux, and dysphagia for statistical analysis. There were no deaths. Mean hospital stay was 5.6 days. Three perforations occurred in group 2 (25%) versus one in group 1 (6%) (not statistically significant). At a mean 27-month follow-up, the dysphagia score was significantly (P < 0.001) improved in both groups but more significantly in group 1 versus group 2 (not statistically significant). Only one patient in group 2 reported heartburn. All patients in group 1 (100%) were satisfied with surgery as opposed to 10 of 13 patients (75%) in group 2 (P < 0.10). Primary laparoscopic Heller myotomy appears to be the treatment of choice for achalasia. Previous endoscopic treatment increases intraoperative complications and may affect long-term results.

Adolescent↗

Robotically assisted laparoscopic radical prostatectomy: feasibility study in men.

PURPOSE: We report our early experience of robotically assisted laparoscopic radical prostatectomy. MATERIAL AND METHODS: Five consecutive patients, with an average age of 58 years, PSA 12, 1.6 positive biopsies, Gleason score 6, were operated in our institution over a period of 1 week by the same surgeon. A robotically assisted laparoscopic nerve sparing radical prostatectomy was performed according to the Montsouris technique with the Da Vinci robot (Intuitive Inc., Mountain View, Calif., USA). RESULTS: The mean installation time was 93 min (range 76-149). The mean operating time (starting at the dissection of the seminal vesicles until the final stitch of the anastomosis) was 222 min (range 150-381 min). The average blood loss was 800 cm(3) (range 700-1,600 cm(3)). No postoperative complications were seen. Bladder catheter time: 6.5 days, hospital stay 5.5 days, urine leak 1/5, continence 4/5, positive margin 1/5. CONCLUSION: After this short experience, we conclude that: The use of a tele manipulation system accompanied by a three-dimensional view of the operating field provides a real benefit for the surgeon, and the urethro-anastomosis is easier to perform. The benefit for the patient is presently not very clear in terms of operating time, postoperative course and functional results, our initial results show that the robotically assisted procedure is at least as safe and effective as the conventional laparoscopic procedure.

Equipment Design↗

Deleterious effects of IL-9-activated mast cells and neuroprotection by antihistamine drugs in the developing mouse brain.

Elevated mean IL-9 serum levels have been observed in human neonates who will later develop cerebral palsy. In earlier studies, using a newborn mouse model of excitotoxic lesions mimicking those described in human cerebral palsy, we found that IL-9 pretreatment exacerbated brain damage produced by intracerebral injections of the glutamatergic analog ibotenate. Among its different cell targets, the Th2 cytokine IL-9 is a mast cell growth and differentiation factor that can cause mast cells to release various substances including histamine. In the present study, we sought to determine whether the deleterious effects of IL-9 in our mouse model were mediated by mast cells through histamine release. All mouse pups were pretreated with intraperitoneal injections of IL-9 or saline between postnatal days (P) P1 and P5. Immunohistochemistry for murine mast cell protease-1 performed on P5 showed an increased density of labeled cells in the neopallium of IL-9-treated Swiss pups as compared with controls. Western blot analysis confirmed the increased murine mast cell protease-1 brain content of IL-9-treated Swiss mice. IL-9 pretreatment had no significant effect on ibotenate-induced excitotoxic brain lesions in mast cell-deficient P5 pups (WBB6F1/J kit(W/W-v)), whereas IL-9 exacerbated these lesions in the control littermates with normal mast cell populations. Finally, cromoglycate or antihistamine drugs significantly reduced ibotenate-induced brain lesions in IL-9-treated Swiss pups. Taken together, these data suggest that recruitment of cerebral mast cells with histamine release may contribute to the exacerbation of neonatal excitotoxic brain lesions produced by IL-9. Neuroprotective strategies targeting mast cells may be useful in some neonates at risk for cerebral palsy.

Animals↗

[Video-assisted thoracoscopic surgery].

We describe our experience with video-assisted thoracoscopic surgery (VATS). Twenty-nine patients were operated on with this technique for various anterior thoracic spinal lesions. There were 6 cases of disc herniation with simple resection, 6 with acute thoracic fractures requiring anterior grafting and stabilization, 7 old fractures and malunions treated by corporectomy, grafting and anterior stabilization in 3, 4 with spinal metastases that were resected and stabilized, 3 with a paravertebral spinal tumor (2 schwannomas and 1 chondroblastoma), and 3 osteoid osteomas that were resected with anterior grafting in one case. Indications for these procedures are specified and the technical considerations discussed for each group of pathologies. We had three complications: one conversion to thoracotomy in a case of spinal metastasis, one pleural effusion, and one incomplete resection of a thoracic disc herniation. We emphasize the need for minimally invasive approaches in spinal surgery.

Adult↗

Trophic response of the intestinal mucosa to inflammation in rats injected with turpentine: a study using pair-fed controls.

The effects of restricted food intake and acute inflammation on the small bowel were studied, Wistar rats (250 g) were given subcutaneous injections of turpentine (TR) and compared to two control groups, at 18, 42 and 66 h. One was fed ad libitum (C), the other was pair fed (PF) with TR. The TR and PF rats showed hypoplasia of the jejunal mucosa with decreased protein and DNA contents at 42 h and 66 h. The hypoplasia resulted in a reduced villus height that was significantly different from the controls at 66 h (C: 468 +/- 17, TR[66] : 376 +/- 20, PF[66] : 258 +/- 2.9 microm, P<0.001). This decrease in villus height was significantly greater in the PF rats than in the TR rats at 66 h. The crypt height/villus height (C/V) ratio in the PF rats was greater than in the TR group at all times. However, the protein and DNA contents in the TR group were significantly higher than in the PF group at 42 h and 66 h (TR/PF[42] : 29.5 +/- 1.9 vs 20.5 +/- 2.0, P< 0.001, [66]: 25.8 +/- 2.0 vs 16.6 +/- 1.3 mg/10 cm, P,< 0.001). Disaccharidase activities (sucrase and glucoamylase) per 10 cm jejunum at 66 h were significantly lower in the PF group than in the control and TR groups (sucrase mU/10cm[66] C : 3090 +/- 144, TR 2683 +/- 479, PF 1969 +/- 144, P,< 0.001; glucoamylase mU/10 cm[66] 237 +/- 25, TR 169 +/- 40, PF 123 +/- 5, P< 0.01). The N-aminopeptidase patterns in the TR and PF groups were similar. These data suggest that dietary restriction during acute inflammation is the main factor causing hypoplasia of the jejunal mucosa. However, acute inflammation has a trophic effect on the morphological and function of the mucosa. This effect is probably due to inflammatory mediators, whose synthesis is stimulated by turpentine.

Acute-Phase Proteins↗

Effects of alimentary intact proteins and their oligopeptide hydrolysate on growth, nitrogen retention, and small bowel adaptation in inflammatory turpentine rat.

The effects of dietary proteins given as whole proteins (WP) or as a peptide hydrolysate (PH) on growth, nitrogen retention, and small bowel adaptation were assessed using two groups of male Wistar rats. Measurements were made 18, 42, and 66 h after acute inflammation induced by subcutaneous injections of 0.125 mL turpentine and in two control groups (n = 12). The two diets had the same caloric, nitrogen, vitamin, and mineral content. The WP diet resulted in better weight gain, nitrogen retention, and small intestinal adaptation by control rats than did the PH diet. Loss of body weight after 18 h of acute inflammation was significantly lower and nitrogen retention significantly higher in animals on the WP diet than in those on the PH diet. Small intestine morphology was maintained with the WP diet, whereas villus height was significantly lower after 66 h, and there were fewer mitoses per crypt in the rats on the PH diet. Glucoamylase activity at all times, and N-aminopeptidase activity at 18 h, were significantly higher in rats on the WP diet. The putrescine (at 42 h) and spermidine (at 18 h) concentrations in the mucosa were higher in the rats on the WP diet. These data suggest that synthetic diets should be tested for their nutritional value during acute inflammation before they are used in human nutrition.

Adaptation, Physiological↗

[Laparoscopic ileo-colic resection in Crohn's disease].

UNLABELLED: The objective was to evaluate the reliability and safety of laparoscopic ileocolic resection for Crohn's disease. PATIENTS AND METHODS: From June 1995 to February 1999, 40 patients underwent a laparoscopic ileocolic resection for Crohn's disease. Fistulizing disease, phlegmons and patients with previous laparotomy were excluded. Early morbidity, postoperative comfort and clinical recurrence were rates evaluated. RESULTS: No intra-operative incident or conversion occurred. Mean operating time was 163 min. Complications occurred in three patients: 1 pelvic hematoma with super-infection, 1 protracted ileus (7 days), 1 venous thrombosis. Opiate analgesics were used for a mean period of 3.1 days. Delay before bowel movements was 3.2 days. Post-operative hospital stay was 8 days. Mean size of the wound was 4.1 cm. Twelve patients (30%) developed long-term clinical recurrence; the mean disease-free interval was 10 months. No patient required secondary re-operation. CONCLUSION: Laparoscopic ileocolic resection was reliable and safe in the treatment of Crohn's ileal strictures. The possible role of this method in the treatment of fistulizing disease or recurrence has to be evaluated.

Adult↗

[Static contrast sensitivity in idiopathic Parkinson disease].

During Parkinson's disease static contrast sensitivity (C.S.) abnormalities are linked to an impairment of the sensitive visual function. C.S. was tested in twelve parkinsonians and 12 controls without neurological and/or ophthalmological pathology, using a Colored Stripes Electronic Generator (GEPCO). Results for parkinsons showed a general deficiency over the spectrum of spatial frequencies, which was statistically significant and particularly pronounced for intermediate frequencies. This study was repeated for three patients: it showed threshold deterioration for two of them, correlated by evolution in the disease, and an improvement for the third patient after introduction of dopatherapy. C.S. is subjected to dopaminergic control. Among parkinsonians. C.S. deterioration may result in an operating failure of both the visual cortex and retina, and is improved by dopatherapy. The Static Gepco contrast sensitivity test is easy to reproduce and can be used easily to monitor the sensory visual defect in parkinsonian patients under treatment.

Aged↗

Small bowel transplantation in children: an immunohistochemical study of intestinal grafts.

Seven children with short bowel syndrome underwent small bowel allografting. Episodes of early rejection were observed in five patients who received a graft from paediatric or adult donors but not in two patients who received a neonatal graft. This study aimed, firstly, to define immunohistochemical parameters accompanying rejection and, secondly, to compare immunohistochemical parameters in neonatal grafts with those in grafts from older donors. An immunohistochemical analysis was performed on 85 intestinal biopsy specimens taken for monitoring the transplant. Acute histological rejection was associated with pericryptic infiltrates of CD3+TcR alpha beta + T cells containing clusters of CD8+ cells, numerous CD25+ cells, and increased numbers of CD68+ macrophages. These changes were associated with the appearance of major histocompatibility (MHC) class II antigens on crypt enterocytes and with an appreciable increase in the expression of E-selectin on mucosal endothelial cells. Immunohistochemistry was useful in predicting rejection by showing the appearance of pericryptic CD25+ T cells 48 hours before the first histological lesions of crypt necrosis. Comparison of neonatal grafts with grafts from older donors did not show any significant difference in the density of CD68+ macrophages or in the endothelial expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or E-selectin. In contrast to grafts from older donors, however, neonatal grafts did not express MHC class II antigens on epithelial cells and contained very low numbers of intraepithelial lymphocytes. These data indicate, firstly, that immunohistochemistry is useful for monitoring intestinal transplants and, secondly, that the better clinical tolerance of neonatal allografts may be related to the lower immunogenicity of the neonatal epithelium.

CD3 Complex↗