Long-term morphological and hormonal follow-up in a single unit on 115 patients with adrenal incidentalomas

We investigated the natural course of adrenal incidentalomas in 115 patients by means of a long-term endocrine and morphological (CT) follow-up protocol (median 4 year, range 1–7 year). At entry, we observed 61 subclinical hormonal alterations in 43 patients (mainly concerning the ACTH–cortisol axis), but confirmatory tests always excluded specific endocrine diseases. In all cases radiologic signs of benignity were present. Mean values of the hormones examined at last follow-up did not differ from those recorded at entry. However in individual patients several variations were observed. In particular, 57 endocrine alterations found in 43 patients (37.2%) were no longer confirmed at follow-up, while 35 new alterations in 31 patients (26.9%) appeared de novo. Only four alterations in three patients (2.6%) persisted. Confirmatory tests were always negative for specific endocrine diseases. No variation in mean mass size was found between values at entry (25.4±0.9 mm) and at follow-up (25.7±0.9 mm), although in 32 patients (27.8%) mass size actually increased, while in 24 patients (20.8%) it decreased. In no case were the variations in mass dimension associated with the appearance of radiological criteria of malignancy. Kaplan–Meier curves indicated that the cumulative risk for mass enlargement (65%) and for developing endocrine abnormalities (57%) over time was progressive up to 80 months and independent of haemodynamic and humoral basal characteristics. In conclusion, mass enlargement and the presence or occurrence over time of subclinical endocrine alterations are frequent and not correlated, can appear at any time, are not associated with any basal predictor and, finally, are not necessarily indicative of malignant transformation or of progression toward overt disease

Idiopathic venous thromboembolic disease is associated with a poorer prognosis from subsequent malignancy

METHODS: We carried out a retrospective study of prognosis in Scottish patients diagnosed with cancer within 5 years after a venous thromboembolism (VTE). RESULTS AND CONCLUSIONS: Prognosis was significantly poorer if a VTE occurred up to 2 years before cancer diagnosis, most notably if the cancer was diagnosed in the 6 months after a VTE

Does weight loss improve semen quality and reproductive hormones? results from a cohort of severely obese men

<p>Abstract</p> <p>Background</p> <p>A high body mass index (BMI) has been associated with reduced semen quality and male subfecundity, but no studies following obese men losing weight have yet been published. We examined semen quality and reproductive hormones among morbidly obese men and studied if weight loss improved the reproductive indicators.</p> <p>Methods</p> <p>In this pilot cohort study, 43 men with BMI > 33 kg/m²were followed through a 14 week residential weight loss program. The participants provided semen samples and had blood samples drawn, filled in questionnaires, and had clinical examinations before and after the intervention. Conventional semen characteristics as well as sperm DNA integrity, analysed by the sperm chromatin structure assay (SCSA) were obtained. Serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and inhibin B (Inh-B) were measured.</p> <p>Results</p> <p>Participants were from 20 to 59 years of age (median = 32) with BMI ranging from 33 to 61 kg/m². At baseline, after adjustment for potential confounders, BMI was inversely associated with sperm concentration (p = 0.02), total sperm count (p = 0.02), sperm morphology (p = 0.04), and motile sperm (p = 0.005) as well as testosterone (p = 0.04) and Inh-B (p = 0.04) and positively associated to estradiol (p < 0.005). The median (range) percentage weight loss after the intervention was 15% (3.5 - 25.4). Weight loss was associated with an increase in total sperm count (p = 0.02), semen volume (p = 0.04), testosterone (p = 0.02), SHBG (p = 0.03) and AMH (p = 0.02). The group with the largest weight loss had a statistically significant increase in total sperm count [193 millions (95% CI: 45; 341)] and normal sperm morphology [4% (95% CI: 1; 7)].</p> <p>Conclusion</p> <p>This study found obesity to be associated with poor semen quality and altered reproductive hormonal profile. Weight loss may potentially lead to improvement in semen quality. Whether the improvement is a result of the reduction in body weight per se or improved lifestyles remains unknown.</p

Improving metabolic health in obese male mice via diet and exercise restores embryo development and fetal growth

Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health.Nicole O. McPherson, Hassan W. Bakos, Julie A. Owens, Brian P. Setchell, Michelle Lan

The incidence of occult cancer in patients with deep venous thrombosis: A prospective study

{Objective. This study was undertaken to assess a potential relationship between idiopathic deep venous thrombosis (DVT) and occult cancer. Design. Prospective study with a 2-year follow-up. Setting. The Angiology Unit of the First Department of Surgery, University of Athens, Greece, a tertiary referral centre. Subjects. Two hundred and ninety-three patients with a first episode of venographically or Doppler-proved DVT were included in the study, of whom 264 were followed up for 2 years. \textbackslash{} Interventions. After an initial extensive diagnostic workup, including routine blood counts and chemistries, erythrocyte sedimentation rate, CEA levels, chest X-ray and abdominopelvic CT scan, all patients were closely followed up and periodically examined. Main outcome measures. The incidence of cancer amongst patients with idiopathic and secondary DVT, and the validity of our screening programme. Results. Cancer was diagnosed in 21 out of 84 patients with idiopathic DVT (25\%) as compared with eight out of 202 patients with secondary DVT (4\%). In 22 out of the 29 cases, cancer was detected during the initial admission, and the remaining seven cases were detected during follow-up. Cancer was diagnosed in 15 asymptomatic, healthy individuals, but only in seven of them was the diagnosis made by CT scan. Conclusion. Occult cancer is fairly common in patients with idiopathic DVT, but the routine use of extensive diagnostic studies for its detection remains to be validated by further prospective studies.

Sex hormone changes in morbidly obese patients after vertical banded gastroplasty

Serum sex hormone levels were measured preoperatively in 57 morbidly obese patients (19 men and 38 premenopausal women) and 12 months after vertical banded gastroplasty. In the male group, there was a significant decrease in estradiol and an increase in follicle-stimulating hormone (FSH), total testosterone and sex-hormone-binding globulin (SHBG). Among female patients, a significant decrease in estradiol, total and free testosterone and an increase in FSH and SHBG was found. Irregular menses present preoperatively in 5 women were corrected after successful weight loss. In conclusion, altered sex hormonal levels and gynecologic abnormalities associated with morbid obesity are corrected with adequate weight loss following vertical banded gastroplasty

Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ of the breast

The expression of oestrogen receptor (ER) protein in invasive carcinoma of the breast and its clinical significance has been extensively evaluated, Little information is available regarding ER expression in ductal carcinoma in situ (DCIS), In this study, 46 formalin-fixed, paraffin-embedded tissue specimens of mammographically detected DCIS were evaluated immunohistochemically for the presence of ER using specific monoclonal antibodies against ER (ER-ICA Abbott Lab), The associations between ER expression and histological type, degree of differentiation and patient menopausal status were evaluated, Positive ER staining was present in 72% of cases, Non-comedo types of DCIS were more frequently ER-positive than comedocarcinoma, ER-positive tumours were inversely correlated with the presence of nuclear pleomorphism, The incidence of ER in pre-menopausal and post-menopausal women was similar, In conclusion, ER expression is present in a considerable percentage of DCIS, and ER-positivity is associated with the degree of differentiation and non-comedo carcinoma variants

The effect of vertical banded gastroplasty on glucose-induced beta-endorphin response

Background. beta-Endorphin is an endogenous opioid involved in the regulation of food intake and obesity as well as in insulin metabolism, In this study, we investigated glucose-induced beta-endorphin, insulin, and glucose responsiveness in morbidly obese patients and the effect of surgically induced weight loss, Methods. Thirty-two healthy, nondiabetic, morbidly obese patients (body mass index over 40 kg/m(2)) and 32 normal-weight controls were studied. Serum levels of P-endorphin, insulin, and glucose were measured under basal conditions and during an oral glucose tolerance test (OGTT) before and 12 months following vertical banded gastroplasty. Results. Preoperative basal levels of beta-endorphin, insulin, and glucose and their responses during OGTT in obese patients were significantly higher compared with those of controls. After surgery, basal beta-endorphin, insulin, and glucose levels decreased significantly compared with preoperative values. Postoperative basal insulin and glucose levels were similar to those in controls, while beta-endorphin levels remained significantly higher than those of controls. A significant reduction in total responses of beta-endorphin, insulin, and glucose during OGTT was also observed; however, postoperative beta-endorphin and insulin responses remained significantly higher than in controls. Conclusion. Morbidly obese patients have an increased glucose-stimulated response of beta-endorphin, insulin, and glucose which is partially corrected with weight loss following vertical banded gastroplasty. (C) 1998 Academic Press

Granulocyte-macrophage colony-stimulating factor improves immunological parameters in patients with refractory solid tumours receiving second-line chemotherapy: Correlation with clinical responses

In this report, we studied the immunorestorative properties of subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with refractory solid tumours receiving second-line chemotherapy. Such patients exhibit abnormal immune responses in vivo and in vitro and, therefore, it was of interest to examine the effect of GM-CSF-induced immunomodulation on clinical response. We examined patients with primary malignant carcinomas (head and neck, n = 10; urogenital tract, n = 17; penis n = 6; colorectal, n = 8) who were treated with carboplatin (JM8), 300 ng/m(2) on days 1 and 22, leucovorin (LV), 200 mg/m(2) plus 5-fluoracil (5-FU), 500 mg/m(2) on days 8, 15 and 29 and four cycles of daily injections with placebo or GM-CSF, 300 mu g/day on days 3-6, 10-13, 17-20 and 24-27. Peripheral blood was collected from the patients one day after the end of each of the four-cycle injections with placebo or GM-CSF, namely on days 7, 14, 21 and 28. Peripheral blood mononuclear cells (PBMC) were tested in the autologous mixed lymphocyte reaction (AMLR) and for natural killer (NK) or lymphokine-activated killer (LAK) cell activity. Cytokine levels in serum were measured by immunoenzymatic (ELISA) assay. A total of 21 patients received a four-cycle regimen with GM-CSF (Group 1) and 20 were similarly treated with placebo (Group 2). All received standard chemotherapy as outlined above. Before GM-CSF treatment, all patients exhibited increased serum levels of interleukin-1 (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and prostaglandin E-2 (PGE(2)) and decreased serum levels of IL-2. Cellular immune responses (AMLR, NK- and LAK-cytotoxicity) were also low in all patients. Five patients from Group 1 had a PR (partial response), 2 patients had CR (complete response), and 14 patients had stable disease. Seven patients from Group 2 showed progressive disease, 3 had a PR and 10 had stable disease. All immune parameters were significantly improved during treatment in Group 1 but remained unchanged or even deteriorated in Group 2. Administration of GM-CSF during treatment of cancer patients with conventional chemotherapeutic drugs results in a marked potentiation of deficient cellular immune responses in vitro and a change towards normalisation of cytokine serum levels. The results reported herein support the use of GM-CSF as immunopotentiator during chemotherapy, but more patients must be studied before definite conclusions can be drawn. (C) 1997 Published by Elsevier Science Ltd