Biomedical subjects
Publications and source records attributed to J M Duclos.
This paper presents the clinical features, imaging methods and treatment of non-secreting adrenal tumours. Adrenal incidentalomas are especially discussed. The main histological types of adrenal non-secreting tumours are evoked. Therapeutic considerations are discussed.
Kidney exeresis, which is usually a simple surgical procedure, may sometimes be uneasy due to multiple difficulties related to the size of the lesion or anatomic presentation. In this chapter, such difficulties and their related complications are considered from a pragmatic angle, in order to identify some practical solutions.
Adrenocortical tumors are rare and mostly non-secreting; their discovery is incidental. When secreting, they produce steroid excess and result in a clinical presentation such as the Cushing syndrome, primary aldosteronism, virilization or feminization syndrome. Such tumors are mostly sporadic but can belong to hereditary syndromes predisposing to tumors. The diagnosis of secreting adrenocortical tumors is based upon clinical presentation and biological data associated with specific biological assessments. Adrenal imaging has been considerably improved with the development of CT scan, which can be completed by MRI if necessary. Most of adrenocortical tumors are adenoma, nevertheless some of them can be malignant and the prognosis of such carcinomas is poor. Management of secreting adrenocortical tumors requires surgery in most of the cases and laparoscopic access is now widely used and provides good results in the treatment of benign tumors.
The methods for diagnosing pheochromocytoma have progressed in 25 years, so changing the clinical, biological and tumoral presentations. The authors compare the features of 199 patients with pheochromocytoma operated between 1975 and 2001 by quartiles. The frequency and known duration of hypertension, plasma adrenaline, the tumour size and proportion of cases which were malignant from the outset, have decreased over the observation period (p < 0.01). The average age and proportion of familial cases or associated with diabetes or those of asymptomatic patients (with incidentaloma), has not changed significantly. The pheochromocytoma were adrenal (104 right, 60 left, 12 bilateral) or ectopic (23) and 13 were malignant from the outset. Over a median 5 year follow-up, 35 pheochromocytomas recurred either in the benign or malignant forms. Recurrences of tumours of the right adrenal were more common than those of the left adrenal gland (p = 0.03). In conclusion, pheochromocytomas are diagnosed earlier, at a stage when the tumours are smaller and less secreting. The higher incidence and recurrence rate of right adrenal pheochromocytoma remain unexplained.
INTRODUCTION: Among the manifestations of Münchausen's syndrome, "neurological" forms may exist. OBSERVATION: We present the case of a patient presenting with urinary retention following treatment for urinary incontinence. The patient had injected himself with infected urine collected from his catheter, in order to create septicemia. COMMENTS: Nephritic colitis, false gall stones, addition of fecal matter or of food and saliva in the urine or the bladder, neurogenic bladder and urinary infections have all been reported as possible manifestations of Münchausen's syndrome. Diagnosis of this syndrome is often delayed and laborious, after repeated hospitalisations, examinations and often aggressive treatment. Its therapeutic management is difficult. Patients, despite proof, deny their deceit and refuse psychiatric care.
Genetic alterations, such as loss of heterozygosity (LOH) at the 17p13 and 11p15 loci and overexpression of the insulin-like growth factor (IGF)-II gene, are associated with the malignant phenotype in sporadic adrenocortical tumors. A high risk of recurrence after surgery for adrenocortical tumors is predicted in cases with regional invasion or distant metastases. However, patients with localized tumors also have a high risk of recurrence. Reliable prognostic markers are required to identify subjects at high risk of recurrence. The aim of this study was to assess the prognostic value of three molecular markers (17p13 LOH, 11p15 LOH, and overexpression of the IGF-II gene) by assessing disease-free survival in a large series of adult patients with sporadic adrenocortical tumors. Adult patients (114) were prospectively followed up from diagnosis of the disease to June 1999 or to death. Malignancy was initially diagnosed in 18 patients (McFarlane stage III: n = 1 and stage IV: n = 17). The remaining 96 patients with localized adrenal disease at diagnosis (stage I: n = 60 and stage II: n = 36) were at risk of recurrence. Histological grade was assessed according to Weiss criteria, and tumors were classified into two groups (Weiss score or=4). Tumor samples were analyzed for LOH at the 17p13 and 11p15 loci and for IGF-II gene mRNA content. 17p13 LOH was a strong predictor of shorter disease-free survival in univariate analysis (P = 0.001; relative risk, 27), as were histological grade (Weiss score >or=4; P = 0.00001; relative risk, 15), 11p15 LOH (P = 0.004; relative risk, 9), tumor size (size >5 cm; P = 0.006; relative risk, 18), and overexpression of the IGF-II gene (P = 0.01; relative risk, 5). In a Cox proportional hazards regression model, histological grade (P = 0.04; relative risk, 4.2) and 17p13 LOH (P = 0.009; relative risk, 21.5) were independently associated with recurrence. Molecular markers, particularly 17p13 LOH, are predictive of long-term outcome in patients with sporadic adrenocortical tumors. In patients who have undergone curative surgery, routine assessment of these tumor markers is a useful complement to histological scoring for predicting recurrence and guiding decisions for subsequent follow-up and management.
To identify preoperative factors associated with 30-day morbidity and mortality after pheochromocytoma surgery, we carried out an external review of the records of all patients undergoing pheochromocytoma surgery from 1975 to 1997 at a single center. One hundred and forty-seven patients, including 23 with malignant tumors at the time of the first operation, underwent 165 operations. Death, resection of a neighboring organ, further surgery, secondary transfer to an intensive care unit, and any events associated with a surgical stay exceeding 10 days were defined as complications. Mortality and morbidity were 4 of 165 (2.4%) and 38 of 161 (23.6%), respectively. Morbidity included 13 spleen resections and hematomas. Spleen complications were not related to tumor location, but were probably due to the operative strategy used, a transperitoneal complete abdominal exploration including both adrenal glands. Complications were independently associated with preoperative systolic blood pressure [odds ratio (OR), 1.14/cm Hg], urinary metanephrine excretion (OR, 1.18/10 micromol x day), and with the number of operations (repeat vs. first operation OR, 5.36). In conclusion, pheochromocytoma resection consistently involves a risk of complications. Spleen damage should be prevented by complete preoperative localization studies and an elective or laparoscopic surgical approach. Careful blood pressure control should help prevent complications. Patients with high secretion tumors and those undergoing repeat intervention are at high risk of complications and should be referred to centers familiar with pheochromocytoma management.
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INTRODUCTION: Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. It is a rare disease. Biochemical tests should be performed only in patients at high risk of pheochromocytoma, and an imaging procedure only in those with positive biochemical tests. CURRENT KNOWLEDGE AND KEY POINTS: The most specific and sensitive diagnostic test for the disease is the determination of plasma or urinary metanephrines. The tumor can be located by computerized tomography, magnetic resonance imaging, and specific scintigraphy. Ten to 20% of pheochromocytomas result from hereditary diseases, including multiple endocrine neoplasia type 2, von Hippel Lindau disease, and neurofibromatosis 1. Familial cases are diagnosed earlier, and are more frequently bilateral and recurring than sporadic cases. About 10% of the cases are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. The probability of a recurrence is positively correlated with the urinary excretion of metanephrines and tumor size. Recurrences are more frequent in cases with ectopic tumors and in those with a low plasma epinephrine to total catecholamine ratio. Patients, especially those with familial tumors or low epinephrine secretion, should be followed-up indefinitely. FUTURE PROSPECTS AND PROJECTS: Treatment for malignant recurrences includes surgery, therapeutic embolization, chemotherapy, and the application of therapeutic doses of metaiodobenzylguanidine. Metyrosine, phenoxybenzamine, or somatostatin analogs may help to control blood pressure and to alleviate symptoms in patients with malignant pheochromocytoma; however such a treatment has no antiproliferative effect.
A survey of 7 surgeons in Paris collected 173 cases of adrenal gland resection using laparoscopes or lomboscopes in 164 patients. Video-assisted surgery techniques were used in the past 4 years for: Conn's syndrome (n = 69), fortuitously observed tumors (n = 39), Cushing's syndrome (n = 24), phyeochromocytoma (n = 18) and Cushing's disease (n = 4). There were 155 unilateral tumors and 9 bilateral tumors in patients with Cushing's disease. This survey showed that conversion rate was 14% and local complications rate 2.4%, mean operative time for unilateral operations was 144 minutes (range 50-240) and 266 minutes (range 125-480) for bilateral tumors. Although this was a retrospective uncontrolled survey, pain relief and hospitalization time were greatly improved over traditional open surgery. The difference between the transperitoneal and the retroperitoneal route could not be evaluated due to differences in the number of patients for which each technique was used. Surgeon experience varied greatly, but it appears that video-assisted adrenal gland surgery is the preferred route due to reduced risk and improved post-operative period. Tumors with a diameter greater than 6 cm and malignant or suspected malignant tumors still require open surgery.
OBJECTIVES: To evaluate diagnostic criteria in primary aldosteronism, we studied the sensitivity and specificity of potassium, renin, aldosterone and the renin/aldosterone ratio in 60 patients undergoing surgery for Conn's adenoma, 50 patients with primary hypertension and 49 normal controls. We also searched for a relationship between these parameters and the blood pressure outcome of surgery. METHODS: The diagnostic value of the tests was quantified using the Youden index after adjustment for receiver operating characteristic (ROC) thresholds. RESULTS: Potassium level in patients was lower than in controls, but in 22%, kaliemia was > or = 3.5 mmol/l and the threshold giving the best Youden index (0.93) was 3.9 mmol/l. The diagnostic power of active renin was low (Youden index 0.28), but the Youden indexes for aldosterone level and the aldosterone/renin ratio in supine position were 0.68 and 0.66 respectively. After a mean follow-up of 8.7 months after surgery, 70% of the patients had normal or improved blood pressure levels. None of the biological parameters evaluated was associated with blood pressure outcome, but age > 55 years was related to unfavorable outcome (sensitivity and specificity 80 and 60%). CONCLUSION: The threshold level requiring a search for an adenoma should be raised. When the potassium level is < or = 3.9 mmol/l the aldosterone/renin ratio should be measured in supine position since it evaluates the dissociation between renin and aldosterone seen in primary hyperaldosteronism. The effect of age on the surgical result emphasizes the importance of early diagnosis.
During the last 15 years 8 patients were diagnosed with renin secreting juxtaglomerular cell tumors among 30,000 hypertensive patients. Clinical characteristics included severe hypertension poorly medically controlled in young patients (mean age 22.3 years) and severe hypokalemia (mean 2.83 mmol./l.). Secondary hyperaldosteronism was present in all cases with a constant elevation of renin activity. Renal vein sampling was only positive in 64% of cases. Selective renal arteriography demonstrated an avascular area in 43% of the patients. Computerized tomography showed the tumor in all cases. Mean tumor size was 24 mm. (range 10 to 50). Conservative surgery was feasible in all patients. Perioperative ultrasonography was used for 3 intraparenchymal tumors. Hypertension and hypokalemia resolved within 1 week after surgery. At a mean followup of 98 months (range 24 to 204) no tumor recurrence was documented.
OBJECTIVES: When abdominal imagery reveals bilateral adrenal tumours, diagnosis and treatment may have severe consequences leading to life-long hormone substitution. We report our series of 12 consecutive cases in order to evaluate the diagnostic procedures and propose an adapted therapeutic strategy. METHODS: Over a 5-year period we observed bilateral adrenal tumours in 12 patients (9 males and 3 females; mean age 49.2 years; range 22-67) among a population of 10,000 hypertensive subjects. Routine laboratory tests and hormonal levels were determined in all 12 patients. Abdominal computed tomography with opacification (n = 12) and magnetic resonance imagery (n = 5) was also performed. Other tests including echography and scintigraphy were performed as needed for diagnosis. All patients underwent laparotomy. RESULTS: Hormone levels were normal in 6 patients and led to the diagnosis of pheochromocytosis (n = 5) and primary hyperaldosteronism (n = 1) in the others. After laparotomy, the pathology diagnosis was bilateral pheochromocytosis (n = 5), bilateral metastasis (n = 2) and benign bilateral adenoma (n = 5). In 5 cases, hormone levels were insufficient for establishing diagnosis before laparotomy. In these cases the pathology diagnosis was benign tumour in 4 and malignant tumour in 1. Images of adrenal masses (metastases) led to the diagnosis of the primary cancer in one case. CONCLUSIONS: Search for pheochromocytosis and primary neoplasia, after eliminating adrenal myelolipoma and pseudotumours on the basis of the tomography images, should be the first exploration of fortuitously discovered bilateral adrenal masses. Exploratory puncture biopsy should be avoided and, for tumours greater than 30 mm, exploratory laparotomy is indicated. Tumours less than 30 mm should be followed echographically for six months to eliminate malignancy. Masses which increase in size should be explored surgically. Until larger series enable a standardized approach, malignancy should always be suspected in non-secreting bilateral tumours of the adrenal glands.
BACKGROUND: von Hippel-Lindau disease is an autosomal dominant disorder characterized by the development of hemangioblastomas in the cerebellum, spinal cord, and retina, renal cell carcinoma and cysts, pancreatic cysts, and pheochromocytoma. METHODS: We have studied a series of 36 French patients affected with von Hippel-Lindau disease pheochromocytoma. Thirty (83%) of them were diagnosed as having von Hippel-Lindau disease because the disease occurred in a familial von Hippel-Lindau disease setting; six (17%) were diagnosed as having von Hippel-Lindau disease because they displayed another characteristic manifestation of that disease. RESULTS: The mean age at pheochromocytoma diagnosis was 29 +/- 14 years (5 to 62 years). Bilateral tumors were documented in 15 (42%) cases, paraganglioma was associated with adrenal pheochromocytoma in four cases, and malignant pheochromocytoma occurred in three cases. Prevalence of pheochromocytoma revealing von Hippel-Lindau disease was 20 (53%) out of 36. In six cases pheochromocytoma was the only manifestation of the disease. CONCLUSIONS: In the interest of the patients themselves and of family members who are at risk, search for von Hippel-Lindau disease must be systematic in the presence of pheochromocytoma. Basic checkup may be completed with familial inquiry, ophthalmoscopy, cerebral magnetic resonance imaging, abdominal ultrasonography, and computed tomography-scan for detection of latent lesions. In the future, after characterization of von Hippel-Lindau disease gene mutations, molecular diagnosis is going to be possible in individual patients.
There are two critical moments for the development of severe infectious complications following transurethral prostatectomy (TURP): the operative and immediate postoperative periods, and the day that the postoperative drainage catheter is removed. To optimize the timing of antibiotic prophylaxis with cefotaxime, two prospective randomized studies were conducted in patients with preoperatively sterile urine. In Study 1, all patients (n = 50) received cefotaxime 1 g intramuscular (i.m.) 1 hour preoperatively and were then randomized to receive either a second identical dose of cefotaxime 1 hour before catheter removal 24 hours later, or no further antibiotic treatment. In Study 2, patients (n = 89) were randomized to receive either cefotaxime 1 g i.m. 1 hour preoperatively or no preoperative antibiotic, after which all received cefotaxime 1 g i.m. 1 hour before catheter removal. Results were compared using identical evaluation criteria for infection in both studies: incidence of fever (temperature > 38 degrees C), bacteriuria (10(5) organisms/mL) and positive blood cultures, and duration of hospital stay (days). In Study 1, infection was significantly reduced with respect to all parameters in the group receiving two doses of cefotaxime, and total drug treatment costs were halved. In Study 2, the groups did not differ with respect to any parameter. We conclude that a single dose of cefotaxime 1 g i.m. 1 hour preoperatively provides inadequate cover for urethral catheter removal 24 hours later, and that prophylaxis with a single dose of cefotaxime 1 g i.m. 1 hour before catheter removal is just as effective as two doses given 1 hour preoperatively and 1 hour before catheter removal. Prophylactic coverage is essential during the action of removing the catheter and the time immediately following the operation. Long-term antibiotic coverage (24 hours or more) is not necessary. Thus, following TURP in patients with preoperatively sterile urine undergoing continuous bladder irrigation for 24 hours postoperatively, the optimal dose schedule for antibiotic prophylaxis with cefotaxime is a single 1-g dose given i.m. 1 hour before catheter removal.
Cells obtained from 6 adult human adrenals or adrenal fragments were cultured in serum-free synthetic medium (McCoy's) in order to study the isolated effects of IGF-I on steroidogenesis and its interactions with ACTH. After addition of peptide, changes in the activities of steroidogenic enzymes were assessed by measuring certain steroids in the spent medium. These included pregnenolone, 17-hydroxypregnenolone (17-OH-Preg), dehydroepiandrosterone (DHA), 17-hydroxyprogesterone (17-OH-P), androstenedione (AD), 11-deoxycortisol and glucocorticoids (chiefly cortisol and its immediate precursors, 11-deoxycortisol and 17-OH-P) and cortisol itself. The steroid responses obtained with repeated doses of IGF-I (40 ng/ml approximately 10(-9) M), added at 0, 48 and 72 h, over 4 days' culture were quite different from those obtained with repeated doses of ACTH (0.25 ng/ml approximately 10(-10) M). All the steroids measured increased with time of culture under the influence of ACTH and, apart from pregnenolone which peaked, tended to reach a plateau. With IGF-I, by contrast, DHA, AD, 11-deoxycortisol and glucocorticoid production increased initially, then decreased progressively, whereas pregnenolone, 17-OH-Preg and 17-OH-P production was either absent or negative. Cumulative steroid production over 4 days reached similar levels in response to a single dose of IGF-I and/or ACTH, with two major exceptions: pregnenolone dropped significantly with IGF-I [46% +/- 6 (SEM) as opposed to 93% +/- 11 with ACTH, P less than 0.005, n = 5], as did 17-OH-P (48% +/- 11 vs 113% +/- 8 with ACTH, P less than 0.001, n = 6). Increased formation of down-stream metabolites (DHA, AD, 11-deoxycortisol and glucocorticoids) would suggest that IGF-I induced stimulation of the 17 alpha-, 21- and 11 beta-hydroxylases. The responses to ACTH stimulation of cells which 4 days previously had been pre-treated with an initial and single dose of IGF-I and/or ACTH emphasized the impact of IGF-I on the 3-hydroxylation steps in cortisol biosynthesis. Compared with ACTH pre-treatment, the effects of which faded in the long term, pre-treatment with IGF-I resulted in a significantly increased steroidogenic response (P between less than 0.05 and less than 0.01). With the single exception of pregnenolone (43% +/- 4.7), production of all the metabolites was amplified: 17-OH-Preg: 348% +/- 88; DHA: 643% +/- 127; 17-OH-P: 193% +/- 36; AD: 725% +/- 200; 11-deoxycortisol: 573% +/- 110; cortisol: 1000%.(ABSTRACT TRUNCATED AT 400 WORDS)
Systematic histological examination of 119 operative specimens of radical nephrectomies performed for renal cell carcinoma revealed adrenal invasion in 6 cases (5.04%). Preoperative computed tomography visualised the adrenal lesions with a sensitivity of 100%. Adrenal involvement was due to either contiguous invasion (3 cases) or metastatic spread (3 cases). Other visceral or lymph node metastases were detected in every case. The mean survival of patients with an adrenal lesion was 16.5 months. These data and those reported in the literature suggest the value of systematic adrenalectomy as part of radical nephrectomy.
Several regimens of antibiotic prophylaxis have been used in transurethral prostatic resection. In this study 50 patients received 1 g of cefotaxime during resection and thereafter were divided at random into two groups: one group received another 1 g dose of cefotaxime when the bladder catheter was removed, while the other group was left untreated at that stage. The administration of cefotaxime during both prostatic resection and catheter removal resulted in a highly significant reduction of infection risk, duration of hospitalisation and cost of antibacterial treatment. The most important risk of sepsis seems to be related to an apparently innocuous procedure: removal of the bladder catheter with resumption of spontaneous micturition.