Evolution of adjuvant treatment in endometrial cancer-no evidence and new questions?

PURPOSE: For endometrial cancer (EC), clinical and pathological risk factors are taken to triage patients and estimate their prognosis. Lymph node involvement (pN+), lymphovascular space involvement (LSVI), grading, age of the patients, and T classification are internationally accepted parameters for treatment decisions. MATERIALS AND METHODS: Studies on adjuvant radiation, chemotherapy, and chemoradiation are discussed against the background of risk stratification and clinical decision-making in early-to-advanced stage endometrial cancer. Recent publications on adjuvant treatment in high-risk disease and its implications for the patients with regard to expected oncologic benefit and treatment-related toxicity are discussed. RESULTS: Surgery is the mainstay of treatment of EC patients. Well-differentiated tumors and early disease (FIGO IA) should be followed up without further treatment. In FIGO I stage without risk factors, VBT remains the standard treatment after surgery. FIGO I, II patients with one or more risk factors (MI ≥ 50%, Grading[G]3, age >60 years, LVSI) benefit from external beam radiotherapy (EBRT) in terms of survival. There are no data of acceptable quality demonstrating that chemotherapy is superior to radiation in locally advanced carcinomas. Therefore, even in locally advanced disease (FIGO III, IV), EBRT remains the standard of care after surgery. EBRT contributes to the very low rate of local relapses and better DFS in these patients and should not be replaced by chemotherapy only. Whether and which subgroups of patients benefit from an additional (concomitant and/or adjuvant) chemotherapy in terms of disease-free survival remains a controversial issue. The recently published PORTEC-3 trial could not create clear evidence. With a high rate of isolated tumors cells and micrometastases in the specimens, the increasing use of unvalidated sentinel concepts in endometrial cancer raises more questions with regard to indications for adjuvant treatment. In the future, integrated genomic characterization of tumors might be helpful for treatment individualization in the adjuvant setting.

Involvement of nitric oxide in corticosterone release and glucose metabolism in food deprived rats.

This study was performed to investigate the involvement of nitric oxide (NO) in corticosterone, endpoint product of hypothalamo-pituitary-adrenal (HPA) axis activation, and metabolic responses to 3 days of food deprivation. To investigate this aim, we used a nonspecific inhibitor of nitric oxide synthases, N-nitro- L-arginine methyl ester (L-NAME). In food deprived group we have noted a significant increase in plasma corticosterone concentration accompanied by a significant depletion in hepatic glycogen content with concomitant increase in glycogen phosphorylase (GP) activity by 63.72%, key enzyme of glycogenolysis and decrease in hexokinase (HK) activity by 25.16%, leading to significant decrease in glucose concentration. However, L-NAME administration in food deprived rats decreased slightly corticosterone level and GP activity (16.39%) and increased HK activity (11.26%) as compared to food deprived group. Considering these results, we can deduce that in food deprivation nitric oxide is involved in the regulation of corticosterone release and in glucose metabolic responses via glycogenolysis activation by the stimulation of GP activity and the inhibition of HK activity. However, more studies are necessary to further clarify the mechanisms by which NO induces these responses.

Vasopressin and nitric oxide synthesis after three days of water or food deprivation.

Nitric oxide has been suggested to be involved in the regulation of fluid and nutrient homeostasis. In the present investigation, vasopressin and nitric oxide metabolite (nitrite and nitrate) levels were determined in plasma of male Wistar rats submitted to water or food deprivation for three days. Hematocrit and plasma sodium showed marked increase in dehydrated and starved rats. Potassium levels and plasma volume decreased in both treated groups. Plasma osmolality and vasopressin levels were significantly elevated in water deprived (362.8 +/- 7.1 mOsm/kg H2O, 17.3 +/- 2.7 pg/ml, respectively, p < 0.001) rats, but not in food deprived (339.9 +/- 5.0, 1.34 +/- 0.28) rats, compared to the controls (326.1 +/- 4.1, 1.47 +/- 0.32). The alterations observed in plasma vasopressin levels were related to plasma osmolality rather than plasma volume. Plasma levels of nitrite and nitrate were markedly increased in both water and food deprived rats (respectively, 2.19 +/- 0.29 mg/l and 2.22 +/- 0.17 mg/l versus 1.33 +/- 0.19 mg/l, both p < 0.01). There was a significant negative correlation between plasma nitrite and nitrate concentration and plasma volume. These results suggest that both dehydration and starvation increase plasma nitric oxide, probably by activation of nitric oxide synthases. The release of nitric oxide may participate in the regulation of the alteration in blood flow, fluid and nutrient metabolism caused by water deprivation or starvation.

Bronchioloalveolar lung carcinoma: results of surgical treatment and prognostic factors.

STUDY DESIGN: To determine the long-term results after surgical treatment of bronchioloalveolar lung carcinoma (BALC) and to identify prognostic factors. PATIENTS AND METHODS: A retrospective study of 70 patients (49 men, 21 women), mean age 61+/-10 years, was carried out. Their carcinomas were classified into three clinicopathologic types: nodular or tumoral, pneumonic, and diffuse types. All the diagnosed BALC cases were reviewed and were classified into histologic types: mucinous, nonmucinous (including fibrotic center), and mixed tumors. Univariate and multivariate analyses were carried out. RESULTS: The nodular or tumoral type was identified in 42 patients, pneumonic in 21, and diffuse in seven. Histologically, there were 36 mucinous, 25 nonmucinous, and nine mixed tumors. Resection was complete in 61 instances (87%) and incomplete in five. The 5-year survival rate was 34% in patients with curative resections. Five prognostic factors were identified by univariate analysis, but in multivariate analysis, only three factors remained significant: the absence of symptoms, the TNM stage, and completeness of resection. Thirty-six patients with curative resection (59%) developed recurrences (in the lung in 26 patients; mediastinal lymph nodes, four; distant metastases, nine). The frequency of recurrence was significantly greater in patients with pneumonic-type BALC than in nodular or tumoral types (p<0.01), and pulmonary recurrences were significantly more frequent in pneumonic than in tumoral types (p<0.02). CONCLUSIONS: This study confirmed that the overall prognosis of BALC is not significantly different from that of the other non-small cell lung cancers. We found that the lungs are the predominant site of recurrence in BALC, especially in the pneumonic types. The complete surgical resection of localized BALC offers the best chances of long-term survival.

Utility of C-reactive protein measurements for empyema diagnosis after pneumonectomy.

Serum C-reactive protein (CRP) levels were studied serially during the postoperative period in 151 consecutive patients who underwent pneumonectomy. Virtually all patients who had a simple postoperative course (115 of 120), as well as 9 patients who had a bronchial infection of the remaining lung, 3 with a pulmonary embolus, and 2 who suffered postoperative bleeding requiring reoperation, demonstrated a similar postoperative evolution in their CRP values: a rapid postoperative rise until a peak or a plateau (mean peak value, 132 +/- 25 mg/L) was reached within 3 to 6 days, followed by a progressive decline to a value of less than 75 mg/L on day 9, and less than 50 mg/L on day 12. Conversely, all 12 patients who suffered empyema postoperatively, as well as 3 patients with bacterial pneumonia, 1 patient with chylothorax, and 1 patient with inflammatory pericarditis, demonstrated either a markedly persistent elevation in their CRP values or a secondary rise in the levels which exceeded 100 mg/L. Because of the high sensitivity (100%) and specificity (91.4%) of the CRP levels in detecting postpneumonectomy empyema, we recommend the routine use of this measure. Furthermore, a low CRP value after pneumonectomy (less than 50 mg/L) may help in deciding whether to confidently discharge a patient from the hospital in the absence of empyema. The negative predictive value of this method was found to be 100%.

Tissue norepinephrine turnover and cardiovascular responses during intermittent dehydration in the rat.

We investigated the central and peripheral sympathetic responses to intermittent dehydration in rats. The norepinephrine (NE) turnover, a biochemical index correlated with noradrenergic neuronal activity, was measured. The modification of blood pressure was also determined by telemetry during the different cycles of dehydration. Dehydration caused a decrease of NE turnover in A2, A5 and A6 nuclei and in peripheral organs. The vasopressinergic level of dehydrated rats decreased in hypophysis and hypothalamus, and increased in plasma. A repeated gradual increase of arterial blood pressure during the first three days of dehydration, followed by a sudden drop when the rats were rehydrated on the fourth day was observed. In conclusion, our study revealed an increase in blood pressure and in central sympathetic activity during dehydration.

[Surgery in small cell anaplastic cancer of the lung]. / La chirurgie dans le cancer anaplasique a petites cellules du poumon.

Surgery has few indications in the treatment of small lung carcinoma. It is currently being evaluated for combined radiotherapeutic/chemotherapeutic treatment strategies.

[Effects of simulated weightlessness on the hypophyseal-cortical-adrenal axis in the pregnant rat]. / Effets de la simulation de la microgravité sur l'axe hypophyso-cortico-surrénalien chez la rate gestante.

The eventual part of stress in the hormonal responses to simulated weightlessness was studied during gestation in the rat. We have compared these responses with the effects of two other situations well-known to provoke stress: ultrasounds and denutrition. An increase of blood and adrenal corticosterone levels was found in mothers after denutrition, neither after ultrasounds nor after simulated weightlessness. In foetuses, a decrease of weight was noted after denutrition and simulated weightlessness. Foetal suprarenal corticosterone remained normal when mothers were submitted to simulated weightlessness. In this group, a decrease in foetal weight was found that could be explained by non suprarenal hormonal factors or by circulation disturbances.

[Adrenal cortex activity in the malnourished newborn rat]. / Activité corticosurrénalienne chez le rat nouveau-né malnutri.

Newborn rats (4 day-old) were subjected to chronic malnutrition through their mothers submitted to an intermittent fasting (one day out of two) during 41 days. These offspring were compared with others undergoing a treatment of a 21 days malnutrition followed by 20 days ad libitum realimentation. Rats whose mothers were nourished ad libitum with a standard diet served as controls. The body growth was hindered by the malnutrition but restored when fasting was followed by realimentation. The weight of the encephalon, the heart and the ovary was unchanged. In contrast, testicle atrophy was observed without correction by realimentation. A corticoadrenal activation characterized by an increase in blood and adrenal corticosterone levels and by an adrenal gland hypertrophy was observed in undernourished animals. A lower response of the adrenal cortex to ether stress (added stress) was also observed. All these perturbations were suppressed when fasting was followed by refeeding.

[Epidemiologic aspects of cerebrovascular accidents in Tunisia]. / Aspects épidémiologiques des accidents vasculaires cérébraux en Tunisie.

We report the results of 3 epidemiological studies of stroke in Tunisia. In Tunis urban population, the crude annual incidence rate of stroke has been estimated at 0.54/1,000 and the prevalence rate at 6 to 14/1,000. The incidence rate adjusted to population at risk (greater than or equal to 45 years old), is around 1.92/1,000. A door-to-door survey conducted in Kelibia, according to a WHO protocol, showed a prevalence rate of 7.2/1,000 when adjusted to population at risk. CT diagnosed infarction and haemorrhage and excluded non-stroke cases (10 p. 100). Cerebral haemorrhage was more frequent than in other published studies (28 p. 100).

[Dispensation of opioids by pharmacists in Tunisia]. / Dispensation des opioïdes par les pharmaciens en Tunisie.

This national survey aims to evaluate opioid availability and prescription by pharmacists in Tunisia and to examine pharmacists' attitude regarding Tunisian law. We surveyed a sample of 300 pharmacists randomly selected from the National Council of Pharmacists list and using the random table. This study started in September 1999 by sending to pharmacists a confidential questionnaire asking about the importance, the rate of sale and the availability of analgesics in their pharmacy. It also tried to determine pharmacists' opinions regarding Tunisian law. A total of 157 pharmacists out of 300 responded to the survey (52 per cent), 95 per cent were working in pharmacies and 15 per cent in hospitals. Analgesics were estimated to be important to very important in their work in 84 per cent and less important in 16 per cent of cases. They were given under advice with great importance in 85 per cent of cases and with less importance in 15 per cent of cases. Analgesic self-medication was frequent in 95 per cent of cases and rare in 4 per cent of cases. Analgesics of levels 1 and 2 were often to always available in 97 per cent of cases and rarely available in 1.5 per cent of cases. Some 84.7 per cent of pharmacists had opioid supplies and 8.9 per cent had no opioids in stock and 6.4 per cent hadn't given a response. 30 per cent of pharmacists think that the 7 days law for opioid prescription should be modified and 66 per cent think it should not, fearing illicit use, fraud and dependance. Pharmacists think that the minimal list of opioids to be stocked in a pharmacy is sufficient because of low demand.

[Pulmonary resections for cancer in the octogenarian]. / Résections pulmonaires pour cancer chez l'octogénaire.

UNLABELLED: More and more elderly subjects are offered for pulmonary resection. The object of this study was to review the results of excision for cancer in octogenarians. PATIENTS: 51 consecutive patients (44 men, 7 women) with a mean age of 82 years (80-91) were operated on. 31 lobectomies, 2 bilobectomies, 13 pneumonectomies, 1 segmental resection and 4 exploratory thoracotomies were carried out. 17 tumours were classed as stage I, 15 as stage II and 15 as stage III. RESULTS: 38 patients (75%) had uncomplicated post-operative periods; the predicted factors for complication were the existence of weight loss and alteration of respiratory function. 2 patients (4%) died in the post-operative phase. Neither the type of operation, the staging or the existence of cardiovascular dysfunction had any influence on the post-operative phase. The level of the survival at 3 and 5 years was 39% and 16% respectively. 30% of the late deaths were related to intercurrent events. CONCLUSIONS: Pulmonary excision may be envisaged in an octogenarian who is in good physical and intellectual state with a limited tumour. This surgery in general is applied to a population which probably only marginally consists of octogenarians but the results here justify their inclusion in the indications for selection.

[Postpneumonectomy syndrome in adults: description and therapeutic propositions apropos of 8 cases]. / Syndrome postpneumonectomie de l'adulte. Description et propositions thérapeutiques à propos de 8 observations.

BACKGROUND: Adult post-pneumonectomy syndrome can be defined as an extrinsic compression of the main bronchus or a lobe bronchus on the aorta resulting from excessive mediastinal deviation after pneumonectomy. PATIENTS: Eight cases in adults are reported. The delay to symptom onset was a mean 34 months. Three patients complained of increased dyspnea and 5 patients experienced a must more rapid course with adult respiratory distress syndrome in 1. Fibroscopy and chest CT confirmed the diagnosis of extrinsic compression of the main bronchus or a lobe bronchus. RESULTS: In the first 2 patients, endoscopic treatment with an endobronchial prosthesis was unsuccessful. The mediastinum was recentered in the following patients using an inflatable prosthesis positioned in the pneumonectomy cavity. Clinical improvement was achieved in all patients. Fibroscopy and chest CT confirmed the reduction in bronchial compression. DISCUSSION: Early diagnosis and mediastinal recentering are required for good outcome. Surveillance after pneumonectomy should include a search for mediastinal deviation and its consequences, particularly concerning the permeability of the remaining bronchi.

[Right subphrenic abscess and bronchial fistula from late trans-diaphragmatic migration of a postoperative abdominal foreign body.(author's transl)]. / Abcés inter-hépato-diaphramatique avec fistule bronchique par migration tardive trans-diaphragmatique d'un corps étranger abdominal post-opératoire.

Late trans-diaphragmatic migration of a postoperative abdominal foreign body followed a left hepatectomy for injury. Operative treatment, by means of the low posterior thoracic approach consisted of partial resection of the right inferior lobe with immediate closure of the diaphragm and subphrenic drainage. The natural history of the course taken by this abdominal foreign body is used as a basis for discussing diagnostic and therapeutic factors, particularly the surgical route of approach.

[Plastic surgery in ambulatory practice]. / La chirurgie plastique en pratique ambulatoire.

We have analysed 283 patient studies operated of ambulatory during the last two years. These patients represent only 12% of the patient group. It's especially a matter of patients operated urgently. The local anaesthesia in the regional local was practised in terms of 90% of cases. The complications where exceptional. We wanted to insist on the necessary guidelines and pitfalls to forget during the practice of that surgery and we wanted to focus on its advantages.

[The effect of age and dehydration on the activity of the vasopressinergic system in rats]. / Effet de l'âge et de la déshydratation sur l'activité de l'axe vasopressinergique chez le rat.

The aim of our work was to study the different blood parameters as well as the activity of the vasopressinergic axis in young and mature male rats under normal conditions and following a 3-day dehydration cycle by water deprivation. Under normal conditions, our study demonstrates higher levels of vasopressin in mature rats as compared to young rats. This could be due in part to the higher blood osmolality in the mature rats. After dehydration, hypovolemia, plasmatic hyperosmolality, hypernatremia and hyperproteinemia cause a stimulation in vasopressin synthesis and release, as seen in results obtained from the hypothalamus, hypophysis and plasma in both young and mature rats. However, the response of the vasopressinergic axis to dehydration is greater in young rats, suggesting a more pronounced sensitivity to osmotic factors.

[Effect of fasting on glycemia and proteinemia in young and adult rats]. / Effet du jeûne sur la glycemie et la proteinemie chez le rat jeûne et adulte.

The aim of Our work has consisted of studying the effects of a severe three-day fast on the evolution of the body weight, on glycemia and on proteinemia among the young and mature male rats. The decrease in body weight which is more marked among young rats after starvation shows that the loss of body mass due to fasting decreases with the age of the rats. The physiological perturbations of nutritive constants that have been recorded during this period of fast show that the mature rat first attacks its non-protein stocks or glucides, which leads to a decrease in its glycemia and in its lipids; whereas the young rat uses its proteins after only three days of starvation because of its small stock of lipids.

[Endobronchial lipomas. Apropos of 16 cases]. / Les lipomes endobronchiques. A propos de 16 observations.

Intrabronchial lipomas are rare and benign tumours. Sixteen cases treated between 1956 and 1988 at the Marie Lannelongue Surgical Centre, Paris, are reviewed. The patients presented with various symptoms such as cough, haemoptysis, infection or dyspnoea. Radiography was abnormal in 15 cases, and the lesion was regularly located at bronchoscopy. Treatment was chiefly surgical. Owing to the slow and silent growth of intrabronchial lipomas, there is a risk of progressive bronchial obstruction resulting in bronchopulmonary lesions. With an early detection, treatment should be as conservative as possible.

Additive effect of diets and training on total insulin-like growth factor-1 (IGF-1) in rats.

OBJECTIVES: Although it is known that circulating levels of insulin-like growth factor-1 (IGF-1) are influenced by both physical exercise and dietary intake separately, there is little information regarding the additive effect of diets and training on IGF-1 regulation. To test this, we examined the combined effect of 30 days of two different diets (high-protein and high-carbohydrate) and exercise training on total IGF-1. MATERIALS AND METHODS: The study was carried out with four groups of rats; the sedentary group with standard diet (SS) (control group), standard diet with exercise (SE), high-protein diet with exercise (PE) and high-carbohydrate diet with exercise (CE). Serum IGF-1, insulin, corticosterone were analyzed. RESULTS: IGF-1 concentrations were decreased by exercise training (p<0.001) and only with protein diet (p<0.05). Physical training, with and without diet, decreased body weight and food intake (p<0.01) and increased corticosterone levels (p<0.05). Carbohydrate diet did not cause major hormonal and metabolic alterations. CONCLUSION: The main result of this study was the decreased levels of IGF-1 in spite of high-protein diet, which is known to enhance IGF-1 secretion, and the little changes with carbohydrate diet. This may be related to the negative energy balance as a result of the catabolic state induced by exercise training and decreased calorie intake in protein diet. Thus, it can be concluded that the caloric restriction, regardless of dietary composition, decreased IGF-1 secretion.