Biomedical subjects

Laurent Brunaud

Publications and source records attributed to Laurent Brunaud.

At least 19 recordsLinked to original sources

PubMed2006

Lack of association between microsatellite instability and benign adrenal tumors.

BACKGROUND: The adrenal gland may give rise to pheochromocytomas, which are catecholamine-producing tumors originating from the adrenal medulla, or to adrenocortical tumors, which derive from the adrenocortical cortex and may be secreting or not. The genetic mechanisms underlying the formation of these tumors include somatic mutations in susceptibility genes, especially in the familial forms, and allelic loss, especially in chromosome 1. AIM: The aim of this study was to investigate a third genetic mechanism by evaluating microsatellite instability using the reference markers (Bat25, Bat26, D2S123, D5S346, D17S250) validated by the National Cancer Institute. Microsatellite loci were analyzed in 32 benign tumors, including 11 pheochromocytomas and 21 adrenocortical tumors, in patients with and without familial syndrome. RESULTS: The different alleles of microsatellite loci were reliably detected by DNA fragments analysis, whereas data obtained after melting-point analysis on the Lightcycler were inconsistent. No microsatellite instability was detected in any tumor. One patient with a unilateral pheochromocytoma showed a loss of heterozygosity for D17S250. A second patient with a MEN-2A syndrome and a two-sided pheochromocytoma exhibited a loss of heterozygosity for D2S123 in the right tumor only and a retention of heterozygosity for all markers in the left tumor. CONCLUSIONS: These results suggest that microsatellite instability, evaluated by the five reference markers of the National Cancer Institute, is not a feature of benign adrenal tumors.

Adrenal Gland Neoplasms↗

PubMed2006

Recombinant human thyrotropin stimulates thyroid angiogenesis in vivo.

BACKGROUND: Endogenous TSH and rhTSH stimulate thyroid growth by a direct effect on thyrocytes. Our hypothesis was that rhTSH may also stimulate thyroid angiogenesis. STUDY DESIGN: A normal human thyroid tissue sample was grafted into the epigastric area of 14 nude mice. Mice were divided in two groups of 7. The first group (treated mice) received rhTSH stimulation (0.014 UI/mouse/day for 3 weeks), while the second group (control mice) had saline. Histological study with special focus on vascular characteristics was performed by image analysis at day 21 for each graft. VEGF immunostaining score, determined by immunohistochemistry, was defined as the percentage of labeled thyrocytes score, plus an intensity score. RESULTS: Thyroid follicles showed signs of increased colloid re-uptake activity in rhTSH group within a larger surface area than controls (p <0.01). Thyrocytes were taller in the rhTSH group (p <0.01). The diameter of capillary vessels was larger and the microvessels expansion more important in the rhTSH group (p <0.02). Relative capillary area, defined as the ratio between capillary area and follicular area, was also higher in the rhTSH group (p <0.02). VEGF immunostaining score was increased in the rhTSH group (p <0.01). CONCLUSION: rhTSH stimulates angiogenesis and local VEGF expression in normal human thyroid.

Animals↗

PubMed2006

Radiofrequency ablation in palliative supportive care: early clinical experience.

We report our early experience with radiofrequency ablation (RFA) in palliative supportive care. The medical files of eight patients were retrospectively reviewed. Four patients had a renal tumor, and nephrectomy was contraindicated in each patient since they had a poor general status. The fifth patient had a local recurrence in the site of a previous nephrectomy with a pancreatic tail extension, and surgical resection was contraindicated because of abdominal carcinomatosis. Two other patients had bone metastasis, one with a painful metastasis of mammary carcinoma in the head of the humerus resistant to radiotherapy, and the other with metastasis of the tibia of cutaneous melanoma. The last patient had a local recurrence of a sacral chordoma. Management, outcomes and complications were evaluated with 13.1+/-0.3 months follow-up. All five patients with renal carcinomas did not have local recurrence. The two patients treated for bone metastases had no pain 8 weeks after RFA and remained stable over time. One complication occurred 2 months after using the procedure to treat the chordoma, and this patient was hospitalized for a fistula between the sigmoid and hypogastric artery false aneurysm and subsequently died. In conclusion, RFA can be a safe and useful adjuvant treatment in supportive care or unresponsive cancer pain patients. However, the destruction of tumoral tissues in contact with sensitive structures using RFA should be done with caution due to potentially severe complications.

Aged↗

PubMed2006

Observation or laparoscopic adrenalectomy for adrenal incidentaloma? A surgical decision analysis.

BACKGROUND: The optimal strategy remains controversial for adrenal incidentaloma, 4 to 6 cm in size, nonfunctioning, and without malignant imaging characteristics. A decision analysis model was used to identify relevant variables for selecting the optimal management (observation versus adrenalectomy). MATERIAL/METHODS: Risk/benefit analysis in tertiary care center. The probabilities of each health outcome states were determined by a review of the literature from 1980 to 2002 (n=2844 patients); and from a retrospective review of experience at University of California San Francisco (UCSF). RESULTS: The baseline probabilities of morbidity after laparoscopic unilateral adrenalectomy and a new indication developing during initial observation (hypersecretion, size increase, malignancy) were 7.8% and 3.1%, respectively. We found observation to be the preferred approach when using baseline probabilities and utilities. Laparoscopic adrenalectomy becomes the preferred approach however if: (1) The morbidity rate from laparoscopic unilateral adrenalectomy is < 3.0%, 2) The probability of a new indication developing for adrenalectomy during observation is > 7.5%, 3) A patient's perspective of observation has a utility of lower than 98.6%, and (4) A patient views having a complication from adrenalectomy is not much deleterious (utility > 88.1%). CONCLUSIONS: This decision analysis model identifies the important variables for selecting the optimal management approach for adrenal incidentalomas. These results can be used to select the optimal management strategy based on individual patient preference and surgeon-specific complication rate.

Adrenal Gland Neoplasms↗

PubMed2005

Long-term results of Delorme's procedure and Orr-Loygue rectopexy to treat complete rectal prolapse.

PURPOSE: The aim of this study was to assess long-term outcome of Orr-Loygue rectopexy and Delorme's procedures in total rectal prolapse management. METHODS: Data were collected retrospectively from 1978 to 2001. Statistical analysis was performed by chi-squared test and Student's t -test. RESULTS: One hundred nine patients underwent either a Orr-Loygue rectopexy (49 patients) or a Delorme's procedure (60 patients). Mean follow-up was 88 (range, 1-300) months. In the rectopexy group, the overall complication rate and the recurrence rate were 33 percent and 4 percent, respectively. In patients with preoperative constipation, this symptom was improved or completely resolved in 33 percent and worsened in 58 percent postoperatively. Seventy-three percent of patients with preoperative incontinence were continent or had continence improvement postoperatively. In Delorme's group, overall complication and recurrence rates were 15 percent and 23 percent, respectively. Mortality was 7 percent. In patients with preoperative constipation, this symptom was improved or completely resolved in 54 percent and worsened in 12.5 percent of patients postoperatively. Forty-two percent of patients with preoperative incontinence were continent or had continence improvement postoperatively. CONCLUSIONS: In this study, Orr-Loygue rectopexy had a lower long-term recurrence rate. However, this surgical procedure is associated with a higher complication rate. We believe that Delorme's procedure is still a valuable option in selected patients with postoperative minimal morbidity but higher recurrence rate.

Adolescent↗

PubMed2005

Transcervical video-assisted resection of Zenker's diverticulum.

We report a novel technique for resection of symptomatic Zenker's diverticulum. Two consecutive patients underwent a transcervical video-assisted dissection and resection of Zenker's diverticular pouch. Both patients exhibited good anatomical and functional results at 10 months follow-up.

Aged↗

PubMed2004

Does robotic adrenalectomy improve patient quality of life when compared to laparoscopic adrenalectomy?

The purpose of this study was to evaluate and compare perioperative quality of life in patients after laparoscopic versus robotic adrenalectomy. From November 2000 through August 2003, 33 consecutive patients underwent laparoscopic (n = 14) and robotic (n = 19) adrenalectomy. Data were obtained prospectively during management and by patient questionnaire (SF36, State-Trait Anxiety Inventory) preoperatively and postoperatively, at day 4 and at 6 weeks. Physical functioning, role limitations due to physical health problems, and bodily pain (Physical SF36 scores) were decreased at day 4 (p = 0.004) in all patients when compared to preoperative levels; and became similar to preoperative levels after 6 weeks. Patients who underwent robotic adrenalectomy had an increased score at 6 weeks of role limitations due to emotional problems (Mental SF36 score) (p = 0.03). No other significant difference was observed between patients after laparoscopic or robotic adrenalectomy. Although state anxiety was decreased postoperatively at day 4 and at 6 weeks (p = 0.01) in all patients, there was no significant difference between laparoscopic and robotic adrenalectomy. Postoperative pain was similar in both groups but had a tendency to be higher when patients underwent a left adrenalectomy (p = 0.07). Similarly, state anxiety had a tendency to be higher postoperatively at day 4 in patients after left adrenalectomies (p = 0.06). This study provides an evaluation of perioperative quality of life in patients after minimally invasive (laparoscopic and/or robotic) adrenalectomy. We observed no major difference between patients who underwent laparoscopic or robotic adrenalectomy. Thus, patients' perioperative quality of life is not a justifiable parameter on which to base promotion of robotic adrenalectomies.

Adrenal Gland Neoplasms↗

PubMed2003

Vitamin B12 is a strong determinant of low methionine synthase activity and DNA hypomethylation in gastrectomized rats.

BACKGROUND/AIMS: The respective influence of folate and vitamin B12 deficiency on MTR activity and transcription, and on DNA methylation is not clearly established. The aim of this study was to assess the respective influence of folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA methylation. METHODS: Sixty-one rats were administered normal diet or diet deficient in choline, methionine, folic acid and vitamin B12. Forty-seven of them underwent total gastrectomy or ileal resection. RESULTS: Low vitamin B12 was observed only in gastrectomized rats. Low folate was observed in rats under deficient diet. Total MTR activity (holo- + apoenzyme) was lowered only with vitamin B12 level <200 pmol/l (p=0.0002), while the ratios of total vs. holo-MTR activity and of transcripts MTR vs. GAPDH (RT-PCR) were unchanged. Vitamin B12 was the single determinant of low MTR (lower quartile, odds ratio=15.75, p=0.0017). Low MTR and low vitamin B12 were the two determinants of DNA hypomethylation (lower quartile) (odds ratio=17.07, p=0.0006, and odds ratio=7.31, p=0.006, respectively). CONCLUSION: Vitamin B12 affects MTR expression by a non-transcriptional mechanism different from a protective effect on MTR proteolysis. It is also a strong determinant of DNA hypomethylation.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2003

Incision length for standard thyroidectomy and parathyroidectomy: when is it minimally invasive?

HYPOTHESIS: Current techniques for open conventional thyroidectomy or parathyroidectomy have evolved to enable a shorter incision (main proposition), and the length of the incision is influenced by objective factors. DESIGN: Case series. SETTING: University referral center. PATIENTS AND INTERVENTION: Retrospective study of the most recent 200 primary consecutive routine thyroid and parathyroid operations (excluding neck dissections). MAIN OUTCOME MEASURES: The length of incision was routinely measured with a ruler before the incision. Univariate and multivariate analysis was performed to distinguish variables affecting length of incision. RESULTS: Mean length of the incision was 5.5 cm for total thyroidectomy, 4.6 cm for lobectomy, and 3.5 cm for parathyroidectomy (P<.001). It was 4.1 cm for bilateral parathyroid exploration, but was reduced to 3.2 and 2.8 cm for unilateral (P<.001) and focal (P<.001) explorations, respectively. By multiple regression analysis, thyroid specimen volume and patient body mass index were independent predictors of incision length in thyroidectomy. Extent of exploration and resident training level were independent predictors of incision length in parathyroidectomy. CONCLUSIONS: Current techniques for open conventional thyroidectomy or parathyroidectomy have evolved to enable a shorter incision. Thyroid volume, patient body mass index, extent of the planned parathyroid exploration, and the resident clinical training stage are important variables for incision length in open operation and should be taken into account when minimally invasive thyroidectomy and parathyroidectomy are evaluated.

Female↗

PubMed2003

Prevention, evaluation, and management of complications following thyroidectomy for thyroid carcinoma.

The rate of complications during thyroid surgery has decreased because of better instrumentation, illumination, and surgical expertise. Despite these improvements, certain patients, those requiring reoperation, those with invasive cancers or with numerous nodal metastasis or recurrent tumors, and those with large substernal goiters have a low but appreciable risk for complications. When planning a thyroid operation, one should perform the operation that corrects these problems and decreases the risk for complications. Localization of at least one parathyroid gland is essential. No surgical procedure can be done, however, without a risk of complications. To decrease these possible risks the surgeon should understand the embryologic development of the thyroid and parathyroid glands, the anatomical position of key structures, and use meticulous operative technique. Experience in performing thyroid operations is essential for the best outcome with the fewest complications.

Humans↗

PubMed2003

Chromosomal aberrations by comparative genomic hybridization in thyroid tumors in patients with familial nonmedullary thyroid cancer.

PURPOSE: Nonmedullary thyroid cancer is the most common form of thyroid cancer and its familial form (FNMTC) is increasingly recognized as a distinct clinical entity. However, the genetic background of FNMTC is still poorly understood and the causative gene(s) have not yet been identified. METHODS: Because comparative genomic hybridization allows for screening of the entire tumor genome simultaneously for chromosomal gains and/or losses without prior knowledge of potential aberrations, we used this technique in thyroid normal and neoplastic samples from FNMTC patients (1) to analyze whether chromosomal aberrations would correlate with inheritance pattern, and/or clinicopathologic features and (2) to compare comparative genomic hybridization (CGH) findings in familial tumors with those already known in sporadic differentiated thyroid cancers. RESULTS: No common germline or somatic chromosomal aberrations were observed in patients with FNMTC because the frequencies and most locations of chromosomal aberrations in familial tumors were also common in sporadic tumors. However, some somatic aberrations were only found in familial tumors (gains in 2q, 3q, 18p, and 19p). Common aberrations in familial tumors corresponded to several locations of candidate genes already reported for sporadic thyroid tumorigenesis. CONCLUSIONS: Our findings suggest that chromosomal aberrations in thyroid tumors in patients with FNMTC are not related to inheritance pattern but rather to tumorigenesis.

Adolescent↗

PubMed2003

Effects of vitamin B12 and folate deficiencies on DNA methylation and carcinogenesis in rat liver.

Deficiencies of the major dietary sources of methyl groups, methionine and choline, lead to the formation of liver cancer in rodents. The most widely investigated hypothesis has been that dietary methyl insufficiency results in abnormal DNA methylation. Vitamin B12 and folate also play important roles in DNA methylation since these two coenzymes are required for the synthesis of methionine and S-adenosyl methionine, the common methyl donor required for the maintenance of methylation patterns in DNA. The aim of this study was to review the effects of methyl-deficient diets on DNA methylation and liver carcinogenesis in rats, and to evaluate the role of vitamin B12 status in defining carcinogenicity of a methyl-deficient diet. Several studies have shown that a methyl-deficient diet influences global DNA methylation. Evidence from in vivo studies has not clearly established a link between vitamin B12 and DNA methylation. We reported that vitamin B12 and low methionine synthase activity were the two determinants of DNA hypomethylation. Choline- or choline/methionine-deficient diets have been shown to cause hepatocellular carcinoma in 20-50% of animals after 12-24 months. In contrast, the effect of vitamin B12 withdrawal, in addition to choline, methionine and folate, induced hepatocellular carcinoma in less than 5% of rats.

Animals↗

PubMed2003

Genetic determinants of folate and vitamin B12 metabolism: a common pathway in neural tube defect and Down syndrome?

One-carbon metabolism is under the influence of folate, vitamin B12 and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C --> T and 1298 A --> C), of methionine synthase (MTR 2756 C --> G), methionine synthase reductase (MTRR 66 A --> G) and transcobalamin (TCN 776 C --> G). The pathogenesis of neural tube defect (NTD) may be related to this metabolism. The influence of the MTHFR 677 C --> T polymorphism reported in The Netherlands and Ireland can be questioned in southern Italy, France and Great Britain. MTRR, combined with a low level of vitamin B12, increases the risk of NTD and of having a child with NTD in Canada, while TCN 776 GG and MTRR 66 GG mutated genotypes associated with the MTHFR 677 CC wild-type are predictors of NTD cases in Sicily. Down syndrome (DS) is due to a failure of normal chromosomal segregation during meiosis, possibly related to one-carbon metabolism. MTHFR 677 C --> T and MTRR 66 A --> G polymorphisms are associated with a greater risk of having a child with DS in North America, Ireland and The Netherlands. In contrast, MTHFR 677 C --> T has no influence on DS risk in France and Sicily, while homocysteine and MTR 2756 AG/GG genotypes are predictors of DS risk in Sicily. In conclusion, NTD and DS are influenced by the same genetic determinants of one-carbon metabolism. The distinct data produced in different geographical areas may be explained by differences in the nutritional environment and genetic characteristics of the populations.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2002

Aldosteronoma.

Aldosteronoma is a surgically curable cause of hypertension. Recent studies have found aldosteronomas to be a more common cause of hypertension than previously thought. At least 2% of patients with hypertension may have an aldosteronoma. More than 50% of these patients are normokalemic because of earlier diagnosis or milder disease, but still benefit from adrenalectomy. Patients with hypertension should be screened for possible primary hyperaldosteronism regardless of their serum potassium level. When used in conjunction with the appropriate laboratory tests, high-resolution computerized tomography scanning helps the surgeon to differentiate accurately between an adrenal adenoma and bilateral adrenal hyperplasia. Focused approach and laparoscopic resection are the norm for the surgical treatment of aldosteronoma.

Adrenal Cortex Neoplasms↗

PubMed2002

Multiple endocrine neoplasia type I.

Multiple endocrine neoplasia type I is a rare autosomal dominant disorder with many endocrine and nonendocrine manifestations. Hyperparathyroidism, islet cell tumors, and pituitary tumors are diagnosed most commonly in these patients. There is controversy regarding treatment of the different manifestations and screening modalities of this disorder because no large series has determined the best therapeutic approach. Our institution advocates early screening with biochemical and radiographic testing in patients with a definite predilection for this disorder. Patients with hyperparathyroidism should undergo early surgical intervention of at least three and a half glands combined with bilateral upper thymectomy through a cervical incision. Although the recurrence rate is high, disease-free survival can be for as long as 30 years. Pituitary tumors are predominantly prolactinomas and growth hormone-releasing tumors. Prolactinomas usually require pharmacologic therapy, whereas growth hormone-releasing tumors are treated surgically. Enteropancreatic tumors should be treated surgically or medically, depending on the hormone secreted. Insulinomas respond well to distal pancreatectomy, with enucleation of the tumor from the head and uncinate process of the pancreas. However, there is controversy regarding the surgical treatment of gastrinomas. Carcinoid tumors should be treated with early surgical intervention. Adrenal lesions are thought to occur in association with pancreatic lesions and commonly have an indolent course. Adrenocortical cancers are uncommon in patients with multiple endocrine neoplasia type I. Skin lesions can be excised when cosmetically unappealing.

Adult↗

PubMed2002

Accuracy of selective venous sampling for intact parathyroid hormone in difficult patients with recurrent or persistent hyperparathyroidism.

BACKGROUND: Preoperative noninvasive localization studies of the neck and mediastinum are beneficial before reoperation. However, the role of selective venous sampling (SVS) for parathyroid hormone (PTH) in reoperative parathyroid surgery has never been clearly defined. The purpose of this study was to evaluate the accuracy of SVS when applied selectively to the subset of patients with indeterminate noninvasive localization studies. METHODS: Between January 1990 and December 2001, 64 of 235 (27%) patients with persistent or recurrent hyperparathyroidism were considered candidates for SVS in addition to noninvasive localization studies. Accuracy of SVS for PTH was retrospectively evaluated. RESULTS: Successful surgical treatment was achieved in 86% of these patients. SVS for PTH yielded true-positive results in 75% of patients and was not useful for the surgeon in 17% (completely false-positive in 12% and indeterminate in 5%). In 2% of patients, SVS identified successfully 1 gland but failed to locate another abnormal gland. In 6% of patients, the location of the abnormal parathyroid tissue remained unknown, and the patients have persistent hyperparathyroidism. CONCLUSIONS: We showed that SVS is clinically useful in patients with persistent or recurrent hyperparathyroidism when the noninvasive localization studies do not clearly localize the abnormal parathyroid glands.

Adolescent↗

PubMed2002

Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor.

BACKGROUND: Radioactive iodine is used to identify and treat recurrent and metastatic thyroid cancer of follicular cell origin. Between 30% and 40% of thyroid cancers are either resistant or become resistant to radioactive iodine. Increased sodium-iodide symporter (NIS) and decreased Pendrin (PDS) activity may be associated with increased radioactive iodine effectiveness. In this investigation the effects of Trichostatin A (TSA), a histone deacetylating inhibitor, on human thyroid NIS and PDS gene expression was investigated. METHOD: Cell lines from papillary, Hürthle, and follicular cell carcinomas were treated with TSA for 72 hours at concentrations up to 100 ng/mL. NIS and PDS gene expression was determined using quantitative RT-polymerase chain reaction. RESULTS: . NIS messenger RNA expression in cell carcinomas was increased 107- (1.8-307) and 217- (5.7-408) fold in papillary, 39- (20-63) and 58- (37-80) fold in Hürthle, and 459- (178-810) and 781- (412-1229) fold in follicular after treatment with 50 and 100 ng/mL of TSA, respectively. PDS messenger RNA expression in cell carcinomas was decreased 0.22- (0.05-0.45) and 0.27- (0.09-0.47) fold in papillary, 0.53- (0.46-0.60) and 0.54- (0.44-0.64) fold in Hürthle, and 0.32- (0.26-0.39) and 0.56- (0.47-0.64) fold in follicular, after the same treatment. CONCLUSIONS: In thyroid cancer cell lines, TSA dramatically increased NIS gene expression and reduced PDS expression. The increased NIS expression and reduced PDS expression may make radioiodine therapy more effective in patients with thyroid cancer, especially when the tumors have no or low uptake of radioiodine.

Carcinoma, Papillary↗

PubMed2002

Chromosomal aberrations by comparative genomic hybridization in hürthle cell thyroid carcinomas are associated with tumor recurrence.

Hürthle cell thyroid neoplasms are classified as variants of follicular neoplasms, but they have distinct clinicopathological features. Chromosomal aberrations by comparative genomic hybridization (CGH) are common in Hürthle cell neoplasms. However, there is currently only limited information concerning the relationship between the chromosomal aberrations by CGH and tumor behavior. We, therefore, investigated chromosomal aberrations in primary Hürthle cell neoplasms (13 carcinomas and 15 adenomas) using CGH and correlated the aberrations identified with tumor node metastasis (TNM) stage, tumor differentiation, capsular invasion, and tumor recurrence. Chromosomal aberrations were found in 62% (8 of 13) of carcinomas and 60% (9 of 15) of adenomas. Overall, common chromosomal gains were found on 5p (29%), 5q (36%), 7 (29%), 12p (14%), 12q (21%), 17p (29%), 17q (32%), 19p (32%), 19q (25%), 20p (21%), 20q (29%), and 22q (18%). Common chromosomal losses were found on 2q (18%) and 9q (18%). Thirty-eight percent (5 of 13) of carcinomas were TNM stage III, 31% (4 of 13) were moderately to poorly differentiated, and 46% (6 of 13) were intermediately to widely invasive. Recurrence occurred in 38% (5 of 13). Carcinomas that subsequently recurred had a greater number of chromosomal gains (9.0 vs. 1.3; <0.005) and had more frequent chromosomal gains on 12q, 19q, and 20p (<0.001), 5p, 7, 19p, and 20q (<0.005), and 12p (<0.01) than those that did not recur. Five of the eight (63%) patients with aberrations developed recurrence, whereas none of the five patients without aberrations developed recurrence. In conclusion, chromosomal gains by CGH on 5p, 7, 12p, 12q, 19p, 19q, 20p, and 20q in Hürthle cell carcinomas are associated with tumor recurrence. Such chromosomal aberrations may be predictive for recurrent disease in patients with Hürthle cell thyroid carcinoma.

Adenoma↗