Radioembolization of hepatocarcinoma with 90Y glass microspheres: treatment optimization using the dose-toxicity relationship.

AIM: Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. METHODS: Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. RESULTS: A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/< 1.1 mg/dL. These results are valid for a 90Y glass microsphere administration 4 days after the reference time. CONCLUSION: Given the low predictive accuracy of 99mTc-MAA on lesion absorbed dose reported by several authors, an optimized TARE with 90Y glass microspheres with lobar injection 4 days after reference time should aim at an absorbed dose averaged over the whole non-tumoural liver of 50 Gy/90 Gy for basal bilirubin higher/lower than 1.1 mg/dL, respectively.

Diagnostic accuracy of percutaneous biopsy in retroperitoneal sarcoma.

BACKGROUND: Percutaneous biopsy is recommended before surgery for suspected retroperitoneal sarcoma (RPS) to confirm the histological diagnosis and guide surgical strategy. The present study aimed to establish the diagnostic accuracy of percutaneous core biopsy with respect to histological diagnosis and tumour grade. METHODS: Data on patients with suspected RPS who underwent percutaneous biopsy followed by surgical resection between 2005 and 2016 at one of two tertiary European sarcoma units were reviewed. Histological tumour type and tumour grade on biopsy were correlated with postoperative histology to evaluate diagnostic accuracy. RESULTS: A total of 239 patients underwent percutaneous core biopsy followed by surgical resection in Milan (163, 68·2 per cent) or Birmingham (76, 31·8 per cent). Diagnostic accuracy varied with histological diagnosis (P < 0·001), but demonstrated overall concordance with final pathology following resection in 67·2 per cent of biopsies (κ = 0·606). The majority of discrepancies occurred in dedifferentiated liposarcoma (DDLPS), owing to under-recognition of dedifferentiation in this group. Concordance between pathology on biopsy and resection improved to 81·1 per cent when DDLPS and well differentiated liposarcoma were grouped together as liposarcoma. Grade on biopsy was concordant with grade on resection specimen in 60·4 per cent of tumours (κ = 0·640). Diagnosis of high-grade tumours on biopsy had a high specificity (98 per cent), and moderate positive predictive value (85 per cent) and negative predictive value (78 per cent). CONCLUSION: A diagnosis of DDLPS or leiomyosarcoma on percutaneous biopsy is highly reliable. High-grade sarcomas can be identified with high specificity, which opens the door to a study on neoadjuvant therapy in these patients.

[Current management of sigmoid volvulus in the tropics]. / Prise en charge actuelle du volvulus du sigmoïde en milieu tropical.

Sigmoid volvulus is a frequent medical emergency in Africa. Diagnosis is mostly based on clinical examination and plain abdominal films. Emergency surgical therapy is required for patients presenting severe clinical and radiographic signs. Sigmoidectomy can be performed in a single stage with immediate restoration of digestive continuity or in two stages with colostomy followed by reconstruction several months later. The choice of technique depends on the patient's general condition and intestinal viability, but should also take into account the morbidity, cost, and social consequences associated with colostomy. For patients without severe signs, the method of choice consists of initial detorsion using an endoscope, if available. This strategy allows elective single-stage sigmoidectomy, which is the preferred procedure. Ideally sigmoidectomy after detorsion should be carried out within a few days during the same period of hospitalization and, if possible, using the celioscopic approach.

Cardiovascular complications of obesity in adolescents.

Obesity is an increasingly important worldwide health problem, representing the major risk factor for coronary heart disease. The increase in the prevalence of obesity, particularly among younger age groups, is likely to have long-term implications for cardiovascular disease (CVD) in the years to come, especially at a young age. Obesity plays a central role in the insulin resistance (IR) syndrome and increases the risk of atherosclerotic CVD. The present review will examine the relationships among cardiovascular risk (CVR) factors during the childhood-adolescence-adulthood transition. In fact, the relation between obesity, in particular visceral obesity and CVD, appears to develop at a relatively young age. The foremost physical consequence of obesity is atherosclerotic CVD, and an intriguing example of obesity-related cardiovascular complications affecting young women is the polycystic ovary syndrome (PCOS).

Growth hormone status in morbidly obese subjects and correlation with body composition.

Morbidly obese subjects are characterized by multiple endocrine abnormalities and these are paralleled by unfavorable changes in body composition. In obese individuals, either 24-h spontaneous or stimulated GH secretion is impaired without an organic pituitary disease and the severity of the secretory defect is proportional to the degree of obesity. The GHRH+arginine (GHRH+ARG) test is likely to be the overall test of choice in clinical practice to differentiate GH deficiency (GHD) patients. Similarly to other provocative tests, GHRH+ARG is influenced by obesity per se. Therefore, a new cut-off limit of peak GH response of 4.2 microg/l in obese subjects has been recently assumed. The aim of the present study was to investigate the reciprocal influence between decreased GH secretion and body composition in a group of 110 morbidly obese subjects, using the new cut-off limit of peak GH response to GHRH+ARG test for these subjects. In our study, GHD was identified in 27.3% of the obese subjects, without gender difference. In GDH obese subjects body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), fat mass (FM), and resistance (R) were higher while reactance (Xc), phase angle, body cell mass (BCM), IGF-I, or IGF-I z-scores were lower than in normal responders (p<0.001). In all obese subjects, GH peak levels showed a negative correlation with age, BMI, waist circumference and FM, and a positive correlation with IGF-I. In the stepwise multiple linear regression, waist circumference and FM were the major determinants of GH peak levels and IGF-I. In conclusion, using the new cut-off limit of peak GH response to GHRH+ARG test for obese subjects, about 1/3 morbidly obese subjects were GHD. GHD subjects showed a significantly different body composition compared with normal responders, and the secretory defect was correlated to different anthropometric variables with waist circumference and FM as the major determinants.

Endothelial dysfunction in PCOS: role of obesity and adipose hormones.

PURPOSE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines. METHODS: A prospective study in 50 young women with PCOS (age: 25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and resistin were measured. RESULTS: PCOS, IMT was increased (P <.01), FMD was decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05), whereas leptin and resistin were not different compared with matched controls. Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and QUICKI correlated positively and negatively with IMT (P <.01). There was a significant negative correlation between adiponectin and IMT (P <.05). These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters. CONCLUSIONS: These data suggest that young women with PCOS have evidence for altered endothelial function. Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin. Both insulin resistance and adiponectin appear to be important parameters. It is hypothesized that the type of fat distribution may influence these factors.

Genetic analysis of the follicle stimulating hormone receptor gene in women with polycystic ovary syndrome.

This study was designed to assess the relationship between mutations in the FSH receptor (FSHr) gene and polycystic ovary syndrome (PCOS) in Italian women. The study population included 50 patients with PCOS and 50 age- and body mass index (BMI)-matched controls. A complete anthropometrical, hormonal and pelvic ultrasonographic evaluation was performed in all subjects. Genomic DNA was extracted from peripheral lymphocytes and then each exon of the FSHr gene was amplified by PCR. The mutation identified was cloned and the functional properties were studied after transient expression in COS-7 cells. Direct sequencing of exons 1-10 of the FSHr gene revealed the presence of a heterozygous AAT/ATT mutation affecting the isoleucine residue at position 411, which was replaced by an asparagine, in the second transmembrane segment (I411N). This mutation was only found in one woman with PCOS and not in her parents. This mutation was not present in 50 age and BMI controls and in another 150 women not affected by PCOS. The functional study after transient expression in COS-7 cells revealed that this I411N had similar functional characteristics with respect to the wild type FSHr (wtFSHr). Genetic analyses of polymorphisms in the human FSHr gene were also performed. All 50 women with PCOS harbored the A307T polymorphic variant, 56% harbored N680S, 30% S680S and 14% N680N polymorphisms. In conclusion, the present study demonstrates that mutations of the FSHr gene are rare in Italian women. The only mutation that we found does not appear to have any pathophysiological significance in PCOS.

Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women.

UNLABELLED: In humans, dehydroepiandrosterone (DHEAS) has been postulated to have anabolic and lipolytic properties that could potentially counteract the catabolic effect of cortisol. DHEAS secretion is reduced in morbid obesity, likely due to hyperinsulinemia, and laparoscopic adjustable gastric banding (LASGB), by inducing considerable and rapid weight loss, reduces insulin levels. To investigate the role of decreased insulin levels after LASGB-induced weight loss on DHEAS levels and on body composition changes, we studied 30 pre-menopausal morbidly obese women (BMI ranging 37-62 kg/m2) before, 6, 12 and 24 months after LASGB. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis; tissue hydration was also assessed by impedance vector analysis. At study ending, the subjects had a total weight loss of 28% of baseline body weight (15% after 6 months). After LASGB, weight loss was mainly due to decreased FM, and TBW, FFM, and body hydration were not significantly reduced. Weight loss was associated with an 82% rise in serum DHEAS already after 6 months while cortisol, cortisol/DHEAS molar ratio, and insulin levels fell by 5.5, 62 and 50%, respectively, after 6, 12 and 24 months (p<0.05). CONCLUSIONS: LASGB associated with a well balanced low-calorie diet permits a satisfactory 2-yr weight loss, sparing FFM and without body fluid alterations. As the result of a stable weight reduction program weight loss is associated to decrease in cortisol, cortisol/DHEAS molar ratio, and insulin plasma levels with marked rise in DHEAS. Higher cortisol/DHEAS molar ratio values at baseline are also associated to lower weight loss after LASGB, with lower decrease in FM and higher reduction in FFM and body cell mass, in spite of no differences in dietary regimes. Cortisol/DHEAS molar ratio is likely to represent a reliable marker of favourable modifications in body composition.

Effects of neridronate treatment in elderly women with osteoporosis.

Osteoporosis is a common disorder, especially among elderly post-menopausal women. Elderly women are often affected by co-morbidities, impaired gastrointestinal function and reduced mobility; therefore, the treatment strategy for their osteoporosis can be difficult. In this randomized pilot study, we have investigated the effects of a 12-month treatment with neridronate on bone mineral density (BMD), bone turnover markers and quality of life (QoL). The study included 40 women (age, 65-80 yr; post-menopausal period, >15yr) from a single osteoporosis centre. Twenty women received a monthly im injection of 25 mg of neridronate associated with a daily dose of 500 mg of calcium and 400 U of vitamin D. Twenty women received calcium plus vitamin D supplements alone. Changes in BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Serum type I collagen C-telopeptide (sCTX), urinary free-deoxypyridinoline (ufDPD), bone alkaline phosphatase (ALP) and serum osteocalcin levels were determined. For the QoL assessment, the Italian version of the SF-36 test was administrated. Spine and hip BMD rose by 6.6 +/- 3 and 4.2 +/- 2.3%, respectively (p < 0.05), after 12 months of neridronate treatment. Markers of skeletal turnover significantly fell already after 3 months of neridronate treatment and decreased progressively thereafter within 12 months. The mean decrease at 12 months ranged from 38 +/- 11% for sCTX to 25.2 +/- 15% for ufDPD (p < 0.001, all). The mean improvement in QoL in the treated group was 45.7% for bodily pain, 37.5% for general health perception, 23.1% for vitality, 18% for emotional role functioning and 12% for physical role functioning. The changes observed in BMD, turnover markers and QoL in the untreated group were ns. The intermittent neridronate administration was easily manageable and well tolerated. In conclusion, neridronate currently represents a valid option for the treatment of osteoporosis, since it helps just as much as oral BPs in the improvement of BMD and in particular conditions it can be even more effective.

Evidence for altered adipocyte function in polycystic ovary syndrome.

BACKGROUND: Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes. METHODS: Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin, adiponectin, and resistin) as well as hormonal parameters and markers of insulin resistance as assessed by the quantitative insulin-sensitivity check index. Body mass index (BMI) was stratified into obese, overweight, and normal subgroups for comparisons between PCOS and controls. RESULTS: Adiponectin was lower (P < 0.05) and resistin was higher (P < 0.05) while leptin was similar to matched controls. Breakdown of the groups into subgroups showed a strong body mass relationship for leptin with no changes in resistin although adiponectin was lower in PCOS, even controlling for BMI. In controls, leptin and adiponectin and leptin and resistin correlated (P < 0.05) but not in PCOS. In controls, all adipocytokines correlated with markers of insulin resistance but not in PCOS. CONCLUSIONS: When matched for BMI status, decreased adiponectin in PCOS represent the most marked change. This alteration may be the result of altered adipose tissue distribution and function in PCOS but no correlation with insulin resistance was found.

Adrenal adenoma and normal androgen levels in a young woman with polycystic ovaries: a case of idiopathic hirsutism?

A case of unusual combination of polycystic ovaries (PCO), adrenal non-functioning adenoma and severe hirsutism in a young woman from Southern Italy is reported here. A 18-yr-old woman was referred to our Department because of oligomenhorrea, acne and severe hirsutism. During evaluation of the cause of her symptoms, PCO and small left adrenal adenoma were revealed. Although adrenal androgen excess has been shown to dysregulate the hypothalamic-pituitary-gonadal axis, causing PCO-like syndrome, normal circulating androgen values were found. Androgens and cortisol levels were completely suppressed by low-dose dexamethasone test, excluding autonomous steroid secretion by the adrenal mass. Normal response of cortisol and adrenal androgens to corticotropin stimulation test permitted the exclusion of functional adrenal hyperandrogenism. Despite normal LH/FSH ratio, anovulatory cycles were revealed by persistently low progesterone values. Glucose and insulin response to oral glucose tolerance test did not differ from those of normal population. The patient showed an improvement of acne and hirsutism on therapy with estro-progestins (EP). In conclusion, despite normal pattern of serum androgens and LH/FSH ratio, this patient had anovulatory cycles and good response to the EP treatment. These findings suggest that ultrasonography evidence of PCO together with anovulatory cycles contributed to her clinical picture whereas adrenal adenoma seemed to have no relevant role. This case report underlines the need of cautious interpretation of imaging results and clinical signs of severe hirsutism, reminding one that the true cause of a medical problem may not be the most evident.

Is ovulation induction still a therapeutic problem in patients with polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases affecting women of fertile age, and is characterized by hyperandrogenism, chronic anovulatory cycles and oligomenorrhea or amenorrhea. Given the repercussions of chronic anovulation on sterility, PCOS is a heavy social burden. Here we describe the procedures used to induce ovulation in PCOS patients, the surgical approach and medical treatments that are still being experimented.