Obesity: a gender-view.

PURPOSE: There is a growing awareness of the importance of understanding gender differences in obesity. The aim of this short review was to revise the current evidence on anthropometric characteristics and nutritional and pharmacological aspects of obesity from a gender perspective. METHODS: A literature search within PubMed was performed. Selected publications related to obesity and gender differences were reviewed. RESULTS: The prevalence of obesity among men is higher than in women, but women have a higher percentage of body fat content compared to men, and gender appears to be an important factor in the manifestation of central (android) or peripheral (gynoid) obesity. In addition, while in most clinical trials, women are still underrepresented, in clinical registration trials of anti-obesity drugs, women are commonly up-represented and gender-specific analysis is uncommon. Considering that adipose tissue is one of the factors affecting the volume of distribution of many drugs, mainly lipophilic drugs, gender differences might be expected in the pharmacokinetics and pharmacodynamics of anti-obesity drugs. Indeed, although Liraglutide 3 mg, a long-acting glucagon-like peptide-1 receptor agonist, and naltrexone/bupropion display lipophilic properties, currently, a gender-dose adjustment for both these drugs administration is not recommended. In addition, despite that predicted responders to treatment offer substantial opportunities for efficient use, especially of expensive new therapies, such as anti-obesity drugs, data on gender differences to identify early responders to both these have not yet been investigated. Finally, bariatric surgery gender disparity reflects healthcare practices. Weight loss similar, but differing effects: women need more correction and face psychology challenges; men have worse physiology and fewer comorbidity improvements. CONCLUSION: Gender differences exist in obesity prevalence and phenotype, body fat distribution, drug efficacy, clinical trial representation, and different secondary effects of bariatric surgery. Gender is an important variable in obesity analysis.

Liraglutide and polycystic ovary syndrome: is it only a matter of body weight?

Despite Polycystic Ovary Syndrome (PCOS) is a very prevalent disorder among women of reproductive age, there is widespread agreement that until now, no pharmacological options are available to tackle the entire spectrum of clinical manifestations encountered in the clinical practice. Obesity and insulin resistance, which commonly characterized this syndrome, prompted the design of studies investigating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) in PCOS. Indeed, a very impressive number of randomized controlled clinical trials (RCTs) and systematic reviews provided robust evidence on the effectiveness of GLP-1RA in PCOS as a new, appealing approach, producing both satisfactory and permanent weight loss, and improvement of insulin resistance at the same time. However, most of the subjects included in the RCTs are PCOS patients with obesity/overweight, whereas a portion of PCOS women, which can even reach 50%, might present a lean phenotype. Moreover, some benefits on clinical and metabolic features of PCOS may not have fully emerged due to the low or medium doses employed in the vast majority of the current studies. Thus, pitfalls in the methodology of these studies have led sometimes to misleading results. In addition, some aspects of GLP-1 beyond weight loss, such as preclinical evidence on GLP-1 effects in directly modulating the hypothalamus-pituitary-gonadal axis, or the effects of GLP-1RA on clinical and biochemical expression of hyperandrogenism, still deserve a greater insight, especially in light of a possible therapeutic use in PCOS women independently of obesity. Aim of this review is to further unravel the possible role of GLP-1 in PCOS pathogenesis, tempting to provide additional supports to the rationale of treatment with GLP-1RA in the management of PCOS also independent of weight loss. For this purpose, the outcomes of RCTs investigating in PCOS the anthropometric and metabolic changes have been treated separately to better underpin the effects of GLP-1 RA, in particular liraglutide, beyond weight loss.

Short-time effects of ketogenic diet or modestly hypocaloric Mediterranean diet on overweight and obese women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive age. It is characterized clinically by oligo-ovulation or anovulation, hyper-androgenism, and the presence of polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardio-vascular and metabolic sequelae, including diabetes and metabolic syndrome. In light of these evidences, the most therapeutic option prescribed to PCOS women with obesity, regardless of the phenotype from the severity of clinical expression, is lifestyle correction by diet and physical activity. PURPOSE: The aim of this study was to evaluate the association between PCOS with KD in overweight and/or obese women with PCOS, and evaluate the possible beneficial effects on metabolic and endocrine parameters, compared to a standard, balanced hypocaloric diet such as Mediterranean diet (MD). METHODS: Participants were assigned to receive, in a 1:1 ratio, one of the two following dietary sequences: KD or MD. In all subjects anthropometric parameters, body composition and metabolic and endocrine parameters were obtained at baseline and after dietetic treatment. RESULTS: Our results showed a significant change in the anthropometric and biochemical parameters in both groups after both diet therapies, with statistically significant differences (p < 0.001). Though, the reductions of all parameters were significantly greater in KD group than in MD group. CONCLUSION: Our results suggest that a reduction of dietary intake of carbohydrates by KD may be considered as a valuable non-pharmacological treatment for PCOS.

Is there any gender difference in epidemiology, clinical presentation and co-morbidities of non-functioning pituitary adenomas? A prospective survey of a National Referral Center and review of the literature.

PURPOSE: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy. METHODS: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated. RESULTS: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ2 = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ2 = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R2 = 0.060; IC 1.00-1.10). Headache (62.8% vs. 31.6%; χ2 = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ2 = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ2 = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI. CONCLUSIONS: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA.

A forensic case of erosive cystitis and septic pulmonary embolism: is there a correlation?

Septic pulmonary embolism (SPE) is an uncommon disease in which a microorganism- containing thrombus causes an inflammatory reaction and a mechanical obstruction in the vascular system of the lungs. Usually it is associated with tricuspid valve vegetation, septic thrombophlebitis or infected venous catheters. We present a rare and fatal case of massive septic pulmonary thromboembolism occurred in a diabetic woman, who complained in previous days dyspnoea, abdominal pain and nausea. Autopsy findings showed evidence of an erosive cystitis, while lungs examination showed total occlusion of pulmonary circulation system due to thrombo-embolic clots. In literature cases report about an association between septic pulmonary thromboembolism and erosive cystitis haven't been reported. So, we here show the first reported fatal case of a septic pulmonary thromboembolism as a lethal evolution of an erosive cystitis.

Oral contraceptives versus physical exercise on cardiovascular and metabolic risk factors in women with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Although oral contraceptives (OCs) are one the most widespread therapy in young polycystic ovary syndrome (PCOS) women and physical exercise represents a crucial first step in the treatment of overweight and obese PCOS, no studies were performed to compare the effects on cardiovascular risk (CVR) of OCs and physical exercise in PCOS. OBJECTIVE: To compare the effects of OCs administration and physical exercise on the CVR, clinical, hormonal and metabolic parameters in PCOS women. METHODS: One hundred and fifty PCOS women were enrolled and were randomized to OCs (3 mg drospirenone plus 30 µg ethinyloestradiol), structured exercise training programme (SETP) or polyvitamin tablets. The intervention phase study was of 6 months. Primary outcome was intima-media thickness (IMT) and flow-mediated dilation (FMD). Secondary outcomes were clinical, hormonal and metabolic changes. RESULTS: A significant reduction of IMT and a significant increase of FMD were observed in the SETP group after treatment. Compared to baseline, in the SETP group, a significant improvement in anthropometric measures, insulin sensitivity indexes, lipid profile, cardiopulmonary function, inflammatory markers and frequency of menses was observed. Oral contraceptives use was associated with a significant decrease of hyperandrogenism and a significant improvement of frequency of menses. Further, OCs use had a neutral effect on CVR risk factors. CONCLUSION: OCs effectively treat hyperandrogenism and menstrual disturbances, while SETP is more effective in improving cardiometabolic profile and cardiopulmonary function in PCOS.

Effects of physical exercise on the female reproductive system.

The excess in physical activity could be closely linked to considerable negative consequences on the whole body. These dysfunctions called as "female athlete triad"' by the American College of Sports Medicine (ACSM) include amenorrhea, osteoporosis and disorder eating. The female athlete triad poses serious health risks, both on the short and on the long term, to the overall well-being of affected individuals. Sustained low energy availability can impair health, causing many medical complications within skeletal, endocrine, cardiovascular, reproductive and central nervous system. On the contrary, several studies have shown, that physical activity improves cardiovascular risk factors, hormonal profile and reproductive function. These improvements include a decrease in abdominal fat, blood glucose, blood lipids and insulin resistance, as well as improvements in menstrual cyclicity, ovulation and fertility, decreases in testosterone levels and Free Androgen Index (FAI) and increases in sex hormone binding globulin (SHBG). Other studies reported that physical activity improved self-esteem, depression and anxiety. Thus, the aim of this review is to elucidate the effect of physical exercise on female reproductive system and viceversa the impact of hormonal status on physical activity and metabolism. In addition this review supports the idea that physical exercise is a helpful tool for the management of obesity, prevention of cardiovascular, metabolic diseases and female reproductive organs related diseases (e.g. breast cancer). When the excess in physical activity leads up to the female athlete triad, it is imperative to treat each component of the triad by employing both pharmacological and non pharmacological treatments.

Endocrine changes (beyond diabetes) after bariatric surgery in adult life.

Bariatric surgery is nowadays an effective therapeutic option for morbid obesity. Endocrinologists may thus have a growing opportunity to diagnose and treat obese patients eligible for surgery in pre- and post-operative phase. This requires a better understanding of endocrine changes caused by either obesity or weight loss surgery. Despite the large number of studies available in literature, only limited well-designed clinical trials have been performed so far to investigate changes of endocrine axes following bariatric procedures. There are still areas of unclear results such as female and male fertility, however, weight loss after bariatric surgery is considered to be associated with favorable effects on most endocrine axes. The aim of this clinical review is to overview the available literature on the effects of weight loss after bariatric surgery on the endocrine systems to suggest the most appropriate pre- and post-operative management of obese patients undergoing bariatric surgery in terms of "endocrine" health.

Clinical and prognostic implications of the genetic diagnosis of hereditary NET syndromes in asymptomatic patients.

Neuroendocrine tumors (NETs) can be sporadic or they can arise in complex hereditary syndromes. Patients with hereditary NETs can be identified before the development of tumors by performing genetic screenings. The aim of the study was to evaluate the clinical and prognostic impact of a preclinical genetic screening in subjects with hereditary NET syndromes. 46 subjects referred for hereditary NET syndrome [22 MEN1, 12 MEN2, 12 Familial Paragangliomatosis (FPGL)] were enrolled and divided in 2 groups (group A, 20 subjects with clinical appearance of NET before the genetic diagnosis; group B, 26 subjects with genetic diagnosis of hereditary NET syndromes before the clinical appearance of NETs). The main outcome measures were severity of disease, prognosis, and survival. The rate of surgery for MEN1-, MEN2-, FPGL4-related tumors was 90% in group A and 35% in group B (p<0.01). Both symptoms related to tumors and symptoms related to therapies were significantly less frequent in group B than in group A (p<0.05). Tumor stage was locally advanced or metastatic in 50% of group A and in no one of group B (p<0.01). The mortality rate was 25% in group A and 0% in group B (p<0.05). An early genetic screening for hereditary NET syndromes results in an improvement in clinical presentation and morbidity. A potential impact of the genetic screening on the mortality rate of these subjects is suggested and needs to be investigated in further and more appropriate studies.

Somatopause: state of the art.

Aging is associated with decay in the somatotroph axis, that has been considered to cause many of the catabolic sequelae of normal aging. The physiological changes that the human body undergoes during aging are similar to those observed in GH deficiency (GHD). Changes of aging are represented by increased fat mass, increased cardiovascular risk, reduced muscle mass, reduced exercise tolerance, decreased strength and impaired quality of life. Some authors conjecture that the elderly could be GH deficient and would benefit from GH treatment. However, the endocrine pattern of aging is distinct from the decrease of GH/IGF-I levels associated with hypopituitarism, although there is not sufficient evidence for a clear therapeutic role of GH treatment during somatopause. So, further studies are needed to evaluate the real benefit of somatotropic treatment in aging. This review is focused on the effects of the somatopause and summarize the potentials for a therapeutic role of the recombinant human GH (rhGH) or of GH secretagogues in aging.

The roles of parathyroid hormone in bone remodeling: prospects for novel therapeutics.

The aim of this review is to focus on the roles of PTH in bone remodeling. PTH plays a central role in regulating calcium-phosphate metabolism and its production increases in response to low serum calcium levels. A continue hypersecretion of PTH, as occurs in primary hyperparathyroidism, leads to bone resorption. On the other hand, there is clear evidence of the anabolic properties of PTH.When administered at a low dose and intermittently, this hormone seems to be able to exert positive effects on bone volume and microarchitecture. The effects of PTH are mediated by PTH/PTH-related protein receptor, a G protein that can activate the cAMP-dependent protein kinase (PK)A and calcium-dependent PKC; the activation of PKA account for most of the PTH anabolic action. The anabolic actions of PTH involve direct effects on osteoblasts and indirect effects mediated by activation of skeletal growth factors (IGF-I) and inhibition of growth factor antagonists, such as sclerostin. PTH enhances the number and the activation of osteoblast through 4 pathways: increasing osteoblast proliferation and differentiation, decreasing osteoblast apoptosis and reducing the negative effects of peroxisome proliferator activator (PPAR)γ receptor on osteoblast differentiation. Moreover PTH enhances the Wnt-ß catenin pathway, that is central to osteogenesis and bone formation, inhibiting sclerostin. Finally, PTH induces the synthesis of IGF-I and, due to its prodifferentiating and pro-survival effects on osteoblasts, this could be a key mediator of PTH effect on osteoblasts. In conclusion, the intermittent administration of PTH has a pleiotropic anabolic effect on bone; further studies about mechanisms of action of PTH could be a starting point to new osteoporosis treatments.

Urinary excretion of 5-hydroxy-3-indoleacetic acid in dystimic/depressed, adult obese women: what correlations to hepatic steatosis?

The synthesis of serotonin at CNS level is influenced by diet. Moreover, insulin resistance is associated with lower serotonin levels. Visceral obesity, strictly linked to hepatic steatosis is specifically associated with mild to severe somatic affective-depressive symptom clusters. Previous data support the view that depression involves serotonergic systems, reflecting low levels of urinary 5- hydroxy-3-indoleacetic acid (5-HIAA). The 24-h urinary excretion of 5-HIAA was evaluated in 76 dystimic/depressed, obese/overweight females, divided into two groups, i.e., on a hyper-caloric diet, associated with a life style characterized by leisure time sedentary behavior (LTSB, 35 women), or on a normo-caloric diet, assisted by program-based strategies aimed at promoting physical activity participation (PAP, 41 women). Beck Depression Inventory (BDI) was carried out to score the severity of dystimia/depression. Anthropometric measures, metabolic indices, severity of hepatic steatosis at sonography and HOMA were studied. Urinary levels of 5-HIAA in controls and PAP groups were comparable with a great overlap, while in the LTSB group the urinary excretion of 5-HIAA was significantly reduced in respect to that of the PAP group and obviously compared to that of the control group, 3.4±1.4 mg/L versus 6.2±2.7 mg/L and 6.4±2.6 mg/L, respectively, ANOVA test, P= 0.001. Among metabolic indices, cholesterol, HDL-cholesterol, triglycerides and uric acid were not able to predict urinary concentrations of 5-HIAA, which were not associated with hepatic steatosis; vice versa, ferritin levels, and mainly HOMA values, were independent predictors of the urinary excretion of 5-HIAA (ß=0.235 and 0.45, respectively). Dystimia/depression severity was negatively predicted by urinary 5-HIAA levels in the sense that the highest BDI values were forecast by the lowest values of urinary 5-HIAA (ß= -0.72).The importance of measuring the 24-h urinary excretion of 5-HIAA in follow-ups could rely on a method simultaneously mirroring the well-being status, the adherence to physical activity, which leads to improved insulin sensitivity, and the eating habits acquired by dystimic/depressed overweight/obese patients. In contrast, the significance of the urinary 5-HIAA is reduced in evaluating the severity of hepatic steatosis, likely because it is a structured process.

Circulating levels of cytochrome C, gamma-glutamyl transferase, triglycerides and unconjugated bilirubin in overweight/obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease, characterized by hepatocyte apoptosis, is distinct in fatty liver and non-alcoholic steatohepatitis, the more severe form. Apoptotic cell death is caspase-dependent and associated with mitochondrial membrane depolarization and cytochrome c release. Adhering to the hypothesis that the exposure of hepatocytes to free fatty acids, resulting in increased ROS production and mitochondrial damage, is balanced by the presence of antioxidant substances, circulating levels of gamma-glutamyl transferase, cytochrome c, triglycerides and unconjugated bilirubin were explored in patients suffering from non-alcoholic fatty liver disease with different severity. One hundred and eighty-six consecutive patients who presented recent ultrasound feature of bright liver without any liver disease of known origin were enrolled, eighty-nine of whom underwent liver biopsy. Forty-five subjects were allocated on the basis of histology in fatty liver group while 44 patients formed the group with non-alcoholic steatohepatitis. A cohort of 27 young, lean, apparently healthy individuals was selected as control group. The levels of gamma-glutamyl transferase were normal or slightly increased, while unconjugated bilirubin concentrations were elevated in all the spectra of non-alcoholic fatty liver disease. Comparing the present results with relevant findings from other studies dealing with diseases characterized by apoptosis, we did not find high circulating levels of cytochrome c in non-alcoholic fatty liver disease. What is more, our patients, categorized as suffering from simple fatty liver or from the more severe non-alcoholic steatohepatitis, had similar levels of cytochrome c and gamma-glutamyl transferase, p=0.19 and 0.11. Serum triglycerides were higher in patients with non-alcoholic fatty liver disease than in the healthy group, p=0.001. These findings likely reflect a balance between oxidative stress and anti-oxidant response rather than a lack of reliability of cytochrome c as a reliable biomarker of mitochondrial damage.

Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome.

BACKGROUND: The cellular abundance of the phosphoprotein enriched in diabetes (PED/PEA-15), a 15 kDa protein related to insulin resistance (IR), is increased in women with polycystic ovary syndrome (PCOS). AIM: To investigate whether metformin (MET) has additive effects on PED/PEA-15 protein levels. MATERIAL/SUBJECTS AND METHODS: This is an open label, prospective clinical study over 6 months. Ten hyperandrogenic obese PCOS women [age: 24.6+/-1.6 yr; body mass index (BMI): 30.7+/-1.2 kg/m(2)] were treated with MET (1250 mg/day). Ten age- and BMI-matched normo-androgenic women were used as controls. Outcome measures are: PED/PEA-15 protein levels, fasting plasma glucose and insulin (FPI), reciprocal index of homeostasis model assessment of insulin resistance (1/HOMA-IR); quantitative insulin sensitivity check index (QUICKI); wholebody insulin sensitivity index (ISI); SHBG; total testosterone; free androgen index (FAI). RESULTS: At baseline FPI and PED/PEA- 15 protein levels were higher, while 1/HOMA-IR, QUICKI, and ISI were lower (p<0.001) in MET group than in controls. After treatment, independently of body weight and hyperandrogenism, FPI, and PED/PEA-15 protein levels decreased (p=0.001 and 0.004, respectively), while, 1/HOMA-IR, QUICKI, and ISI increased (p<0.001). PED/PEA-15 protein levels correlated significantly with ISI either before (r=0.636; p=0.048), and after treatment (r=0.758; p=0.011). CONCLUSIONS: PED/PEA-15 protein levels reduced after a short course of treatment with MET in a group hyperandrogenic obese PCOS women. This effect was independent of body weight and hyperandrogenism, and correlated with ISI, thus adding a further benefit to obese PCOS women.

Subclinical myopathy in patients affected with newly diagnosed colorectal cancer at clinical onset of disease: evidence from skeletal muscle biopsies.

OBJECTIVE: To evaluate skeletal muscle biopsy from asymptomatic patients affected with newly diagnosed colorectal cancer and to identify pathological features which may be indicative of tumor-associated muscle disorders, potentially leading to cachexia. METHODS: Patients affected with newly diagnosed colorectal cancer at clinical onset of disease underwent biopsy of the rectus abdominis muscle during elective laparoscopic tumor resection, before chemotherapeutic treatment. Morphometric analyses, ATPase histochemistry and immunohistochemical studies using antibodies directed to N-CAM and to MHC-emb, two sound makers of muscle denervation and injury-induced muscle regeneration, were performed on intraoperative muscle biopsies from ten patients. Muscle biopsies from rectus abdominis of seven subjects affected with non-neoplastic condition, which underwent laparoscopic surgery, were used as controls. RESULTS: In patients' biopsies, we observed a surprisingly high percentage of myofibers with internalized or central nuclei compared to controls (9.15 +/- 8.9 versus 0.6 +/- 0.9, p<0.0003). In addition, in the 30% of patients, small myofibers expressing the MHC-emb have been identified (0.4 +/- 0.5 positive fibers/mm(2)), while in 50% of patients, larger fibers positive for N-CAM have also been detected (0.7 +/- 1.1 positive fibers/mm(2)), suggesting that investigated muscle biopsies exhibit other evidence of muscle fiber injury/regeneration and/or denervation. Among the 10,000 analysed myofibers in control biopsies, no MHC-emb and N-CAM-positive muscle fibers have been detected. Thus, patients affected with newly diagnosed colorectal cancer at clinical onset of disease display early signs of a subclinical myopathy. DISCUSSION: Factors and mechanisms of this cancer-associated myopathy are yet unknown. The facts that the great majority of the abnormally nucleated myofibers are of the fast type and that regenerating myofibers are present, suggest a myogenic response to the colorectal cancer and not to the laparoscopic modalities of the biopsy harvesting. Follow-up of the patients will elucidate the clinical relevance of our observation, and further studies investigating the molecular mechanism underlying this early cancer-associated myopathy will hopefully provide some pathogenetic clues leading to the identification of potential specific targets for therapeutic intervention to prevent tumor cachexia.

Extensive anal condylomatosis: prognosis in relation to viral and host factors.

OBJECTIVE: To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences. METHOD: Clinical data, treatment modalities and follow-up were recorded and analysed in relation to host and viral type. Histology, immunohistochemistry and molecular analyses for HPV search and typing were performed on formalin-fixed paraffin-embedded samples. RESULTS: Sixteen patients [14 males, median age 41.8 years (range 19-66)] affected by extensive anal condylomatosis [10 Buschke-Lowenstein Tumors (BLT) and 6 condylomatosis] treated in three different Italian institutions were included. There was associated preoperative anal intraepithelial neoplasia grade 3 (AIN3) in one and invasive carcinoma in three patients. After radical resection (n = 16) recurrence occurred in 4/10 (40%) BLT patients. Malignancy before or after treatment developed in 5/16 (31.25%) patients. HPV sequences were present in all the samples of 15 evaluable patients (types 6 or 11, 9 patients; type 16, 6 patients). A statistically significant association was found between presence of HPV type 16 and both malignancy and recurrence. Viral variant L83V was present in 3/4 HPV 16 positive recurrent cases. CONCLUSION: Radical resection resulted in a favourable clinical course. Typing of HPV sequences in the management of patients affected by extensive anal condylomatosis may be useful.

Appropriate use of stimulation tests and insulin-like growth factor-I in obesity.

Obesity is characterized by abnormal GH secretion, with GH levels reduced up to levels that are comparable to those found in adult patients with organic GH deficiency (GHD). Despite the marked GH insufficiency, obese patients with no evidence of pituitary disease have generally normal levels of total IGF-I but increased levels of free IGF-I. Although the mechanism of the low GH in obesity is not completely understood nor is it clear whether its relationship with visceral adiposity is causal, it is widely accepted that the low GH secretory state in obesity is reversible since it is completely reversed by the normalization of body weight. Since overweight and obesity might affect the GH response to all provocative stimuli, particular attention has been recently paid to the confounding effect of body weight on the interpretation of GH stimulating tests and appropriate cut-offs for lean, overweight, and obese subjects must be used in order to avoid false-positive diagnoses of severe GHD in obese adults. As the definition of appropriate criteria for the correct diagnosis of GHD in obesity is still debated, and the beneficial effects of chronic recombinant human GH replacement on obese individuals have not been definitely proved yet, further studies are therefore mandatory to confirm the real effectiveness of GH supplementation in conditions associated with a blunted GH secretion without organic hypopituitarism and to understand the physiological relevance of "functional" GHD on the pathogenesis of the multiple maladaptative endocrine changes involved in the pathogenesis of obesity.

Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender.

GH deficiency (GHD) in adults is accompanied by reduced bone mass that may revert only after 2 yr of GH replacement. However, it is unclear whether the gender may modify bone responsiveness to GH replacement in adults. In this study we have evaluated whether bone mineral density (BMD) and turnover improve after GH replacement according to patients' gender. BMD at lumbar spine (LS) and femoral neck (FN), serum osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) were assessed in 64 hypopituitaric patients (35 men, 30-50 yr) before and 2 yr after the beginning of GH replacement. Values of IGF-I and BMD at LS and at FN were expressed as Zscores. At study entry, IGF-I and BMD resulted similar among men and women with GHD. During GH replacement, IGF-I levels increased in both men and women without any difference in the percentage of IGF-I increase between the genders (p=0.47). In women receiving estrogen replacement, however, the percentage of IGF-I increase (p<0.05), and the Z IGF-I score (p<0.001) were significant lower than estrogen untreated women, although IGF-I levels were similar in the 2 groups (p=0.53). The GH dose adjusted for body weight required to restore normal age- and sex- matched IGF-I levels was lower in men than in women (p<0.001), and was higher in women receiving than in those not receiving estrogen replacement (p<0.05). In contrast, hypogonadal men treated with testosterone and eugonadal men received a similar GH dose (p=0.97). Also OC, Ntx levels, lumbar and femoral BMD improved (p<0.001) in all patients. Nevertheless, a greater increase in lumbar BMD increase was observed in men than in women (8.0+/-2.1 vs 2.6+/-0.4%; p<0.05). No significant difference was revealed in bone parameters in women treated or untreated with estrogen replacement and in men treated or not with testosterone replacement for concomitant hypogonadism. At the multiple correlation analysis, gender was a stronger predictor for the required GH dose than the age (p<0.001 and p=0.02, respectively). In conclusion, a 2-yr GH replacement normalizes IGF-I levels, increases bone mass and improves bone turnover both in men and in women with GHD without any difference between the 2 groups, provided that the dose of GH was modulated on the basis of IGF-I levels. Women receiving oral estrogens should receive a GH dose approximately doubled, as compared to men and women not receiving oral estrogens, to achieve similar effects on bone density and turnover. In particular, GH replacement dose, to be successful on bone mass and turnover, depends on gender in hypopituitary patients aged below 50 yr.

Colpocystodefecography in obstructed defecation: is it really useful to the surgeon? Correlating clinical and radiological findings in surgery for obstructed defecation.

OBJECTIVE: Colpocystodefecography images the pelvic floor with the dynamics of defecation, but various authors claim that it overestimates clinical findings. The aim of this study was to evaluate the pre- and postoperative consistency between clinical and colpocystodefecographic findings in patients undergoing surgery for obstructed defecation. METHOD Between June 2001 and September 2003, 20 patients underwent transvaginal posterior colpoperineorrhaphy and rectal mucosal prolapsectomy with one circular stapler for symptomatic rectocele and concomitant anorectal prolapse. They were prospectively evaluated both before surgery by designed questionnaire on constipation and incontinence, proctological, gynaecological and urological examinations, colpocystodefecography and anorectal manometry, and after operation at 6 months by questionnaire and a proctological check-up. The mean follow-up was 30 months (24-48 months). RESULTS: At 6 months the questionnaire revealed a major response in terms of symptoms. The proctological visit confirmed the absence of rectocele in 19 (95%) patients, while the anorectal prolapse had completely disappeared in 17 (85%) patients. Postoperative colpocystodefecography demonstrated a general reduction in the dimensions of the rectocele, which had completely disappeared in five (25%) patients; 40% of the patients had a persistent anorectal prolapse. CONCLUSION: Preoperative data analysis showed a statistically significant correlation between clinical and radiological findings. Postoperatively the global clinical assessment correlated well with patient satisfaction, while there was evidence of a statistically significant difference between the radiological and clinical findings. Routine postoperative use of colpocystodefecography is unjustified unless there is clinical evidence of surgical failure.

Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery.

BACKGROUND: Perioperative nutrition for patients undergoing colon surgery seems to be effective in reducing catabolism and improving immunologic parameters. A relatively low-fiber and highly absorbable diet may facilitate the intestinal cleansing and loop relaxation fundamental for laparoscopic surgery with a lower dose of iso-osmotic laxative. METHODS: From 1 February 2004 to 30 July 2005, 28 patients referred to our unit with colon disease (neoplasms and diverticular disease) amenable to laparoscopic surgery were prospectively randomized into two groups of 14 patients each. For 6 days preoperatively, the patients in group 1 were given 750 ml/day of a diet enriched with arginine, omega-3 fatty acids, and ribonucleic acid (RNA) associated with low-fiber foods. They had 1 day of intestinal preparation with 3 l of iso-osmotic laxative. On postoperative day 2, they were fed orally with the same diet. The patients in group 2 preoperatively received a low-fiber diet. They had 2 days of preparation with iso-osmotic laxative (3 l/day). On postoperative day 3, oral nutrition was restored. Intraoperatively, we evaluated loop relaxation and intestinal cleanliness. Clinical trends were monitored in both groups, as well as adverse reactions to early nutrition. The nutritional (albumin, prealbumin) and immunologic (lymphocyte subpopulations, immunoglobulins) biohumoral parameters were evaluated at the first visit, on the day before surgery, on postoperative day 7, and 1 month after surgery. RESULTS: The two groups did not differ in terms of age, gender, distribution of disease, or baseline anthropometric, biohumoral, or immunologic parameters. There was a significant increase in CD4 lymphocytes on the day before surgery as compared with baseline parameters (p < 0.05) in group 1, but not in group 2. There was no statistically significant difference between the two groups in intestinal loop relaxation or cleanliness or in postoperative infectious complications. CONCLUSIONS: Perioperative immunonutrition proved to be safe and useful in increasing the perioperative immunologic cell response. It may contribute toward improving the preparation and relaxation of the intestinal loops despite the shorter intestinal preparation.