Palliative care in patients with ovarian cancer and bowel obstruction.

OBJECTIVE: Malignant bowel obstruction (MBO) is usually a pre-terminal event in patients with ovarian cancer. However, because of the lack of data in literature, decisions around surgical intervention, non-resectional procedures, or medical treatment of MBO in patients with ovarian cancer cannot be lightly undertaken. We analyzed medical and surgical procedures, performance status, nutritional status, cachexia, and their prognostic value in this group of patients. METHODS: We retrospectively selected all consecutive patients with recurrent ovarian cancer who received medical or surgical treatment for MBO between October 2008 and January 2014 at the Academic Department of Gynecological Oncology of Mauriziano Hospital of Turin (Italy). RESULTS: We found 40 patients: 18 of them underwent medical treatment and 22 of them were submitted to surgery. In the group of surgery, the hospitalization was shorter (p 0.02), the pain reduction was more effective (p 0.001), the number of chemotherapy lines was higher (p 0.03), and re-obstruction was more rare (p 0.02). Between the two groups, we did not find any differences in post-palliation episodes of vomit (p 0.83), type of diet (p 0.34), ability to return home (p 0.72), and death setting (p 0.28). Median survival after palliation was longer in the group of surgery (p 0.025). Cachexia, low performance status, and poor nutritional status were significant predictors of worse survival after MBO, independently by the treatment. CONCLUSIONS: Surgery has to be considered in patients without serious contraindications; otherwise, a medical protocol, including antisecretory drugs, is the standard of care in frail patients.

Simple lifestyle recommendations and the outcomes of gestational diabetes. A 2 × 2 factorial randomized trial.

The benefits of exercise and behavioural recommendations in gestational diabetes mellitus (GDM) are controversial. In a randomized trial with a 2 × 2 factorial design, we examined the effect of exercise and behavioural recommendations on metabolic variables, and maternal/neonatal outcomes in 200 GDM patients. All women were given the same diet: group D received dietary recommendations only; group E was advised to briskly walk 20-min/day; group B received behavioural dietary recommendations; group BE was prescribed the same as B + E. Dietary habits improved in all groups. In a multivariable regression model, fasting glucose did not change. Exercise, but not behavioural recommendations, was associated with the reduction of postprandial glucose (p < 0001), glycated haemoglobin (HbA1c; p < 0.001), triglycerides (p = 0.02) and C-reactive protein (CRP; p < 0.001) and reduced any maternal/neonatal complications (OR = 0.50; 95%CI=0.28-0.89;p = 0.02). In GDM patients a simple exercise programme reduced maternal postprandial glucose, HbA1c, CRP, triglycerides and any maternal/neonatal complications, but not fasting glucose values.

Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.

Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.

Should we consider gestational diabetes a vascular risk factor?

Few and contrasting data have reported vascular endothelial dysfunction and increased serum levels of endothelial dysfunction and inflammatory markers in women with previous gestational diabetes mellitus (pGDM). We aimed at evaluating 6.5 years after delivery: intimal medial thickness (IMT), and C-reactive protein (CRP), interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) levels in 82 non-pregnant pGDM and 113 control women without pGDM. A subgroup of 21 women, taken from the pGDM group, showing current normal BMI, and no metabolic abnormalities, was separately analysed. All the subjects were free of medication and non-smokers. Women with pGDM, independently by their current BMI and presence of metabolic abnormalities, showed significantly higher E-selectin, ICAM-1 and IMT values than controls. IMT proved to be significantly associated with pGDM in a regression model, after adjustments for BMI, waist circumference, blood pressure, and glucose values (beta=0.046; 95% CI 0.028-0.064). In all pGDM women, E-selectin, ICAM-1, IL-6 and hs-CRP values were significantly associated with IMT in the same model. Post-GDM women, despite being currently free from metabolic abnormalities, showed higher values of markers of endothelial dysfunction and IMT than controls, consistent with an increased future cardiovascular risk.

[Leptin as a possible marker of augmented metabolic risk during pregnancy]. / La leptina come possibile marker di aumentato rischio metabolico in gravidanza.

AIM: Leptin is a proteic hormone, isolated in 1994, mainly synthetized in the white adipose tissue. Aim of this study was to compare leptin concentrations in normal pregnancies with those measured in pregnancies complicated by gestational diabetes or gestational hypertension or pre-eclampsia. METHODS: We enrolled 48 pregnant women: 18 with uncomplicated pregnancy, 11 with gestational diabetes, 19 with gestational hypertension or pre-eclampsia. Leptin concentrations were measured in maternal serum at enrollment, together with insulin and cortisol, at delivery and in the immediate postpartum. At delivery serum leptin was calculated in the cord blood too. RESULTS: Fasting plasma leptin and insulin were higher in the group of patients with gestational hypertension, than in the other groups. Third-trimester maternal leptin concentrations correlated significantly with insulin levels in the group of women with gestational diabetes and in the group with gestational hypertension or pre-eclampsia, but not in the women with an uncomplicated pregnancy. CONCLUSIONS: Leptin concentrations in pregnancies complicated by hypertensive disorders are significantly higher than in normal pregnancies. The increased leptin concentrations are independent of associated proteinuria, as women with simple gestational hypertension and preeclampsia showed comparable third-trimester leptin concentrations. In both women with gestational diabetes and women with hypertensive disorders, serum leptin correlated closely with serum insulin, suggesting that the association between leptin and insulin resistance is preserved in pregnancy. Whatever the reasons for an increased maternal leptin production in pregnancies complicated by hypertension, maternal leptin homeostasis does not seem to influence foetal serum leptin concentrations, which seems to be mainly related to birth weight.

Comparison of two enzyme immunometric assays to measure tumor necrosis factor-alpha in human serum.

BACKGROUND: Tumor necrosis factor-alpha is a 17.5 kDa, 157 amino acid protein that is a potent lymphoid factor, which exerts cytotoxic effects on a wide range of tumor cells and other target cells. TNF-alpha has been suggested to play a pro-inflammatory role by influencing transendothelial migration of monocytes and elicits the expression of proteolytic enzymes by macrophages and smooth muscle cells within the atherosclerotic plaque. METHODS: We compared two methods for the quantitative determination of human tumor necrosis factor-alpha in serum samples. Either kit follows the same assay procedure. Serum samples do not need to be diluted before sampling. Standard is provided lyophilized and serial dilutions after reconstitution generate the standard point curves. The tests are enzyme immunometric assays based on a standard 96-well microtiter plate. The wells are coated with anti-human TNF-alpha antibody. RESULTS: The range of the standard curve is similar in both kits. It spans from 1000 through 15.6 pg/mL. The median TNF-alpha concentration in samples measured by Pierce assay (n=368) was 4.23 pg/mL, (range, 1.34-77.2 pg/mL). A very different median was obtained for the same specimen measured with the Titerzyme EIA (median, 176.96 pg/mL; range, 54.7-283.9 pg/mL; n=364). Substantial significant differences were observed between the two methods. CONCLUSION: Our results show that the two kits are unmatchable for results they can give when TNF-alpha concentrations are measured in serum samples. One reason of this disagreement could be the matrix effect or a cross-reactivity of one of the two methods. This study shows that the determination of human serum TNF-alpha needs to be standardized, especially when a comparison of results is required.

C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia.

OBJECTIVES AND STUDY DESIGN: Increasing evidences support an inflammatory origin for gestational hyperglycemia. This paper aims at investigating, cross-sectionally and prospectively, the relationships between tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) levels in normoglycemic and hyperglycemic pregnancies of women with and without conventional risk factors for gestational diabetes (GDM). RESULTS: Both at simple and multiple correlations TNF-alpha levels are associated to fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) values and gestational hyperglycemia, while high sensitivity CRP (hsCRP) levels to body mass index (BMI). Furthermore, the TNF-alpha levels of the second trimester and their increments in the third trimester are significant predictors of insulin levels measured at 32-36 weeks in the subgroup of hyperglycemic women with < or = 35 yr, BMI <25 kg/m2 and the absence of a first-degree relative with Type 2 diabetes (respectively, beta=1.1; 95%CI 0.66-1.48; p=0.002 and beta=1.0; 95%CI 0.36-1.66; p=0.02), in a multiple regression model, after multiple adjustments. In a second cohort of women at low risk for GDM (<25 yr, BMI <25 kg/m2 and absence of a first-degree relative with Type 2 diabetes), 24-28 weeks TNF-alpha levels are highly associated with corresponding insulin and HOMA values in the same model (respectively, beta=0.27; 95%CI 0.11-0.43; p=0.001 and beta=0.30; 95%CI 0.14-0.46; p<0.001). CONCLUSIONS: The data support the developing hypothesis that low-grade systemic inflammation is associated to GDM, in particular for pregnant women without conventional risk factors for gestational hyperglycemia, whose insulin resistance seems less explainable.

Prior gestational hyperglycemia: a long-term predictor of the metabolic syndrome.

Little is known about the association between prior gestational hyperglycemia of different severity and the subsequent risk for the metabolic syndrome. Eighty-one women with prior gestational diabetes mellitus (GDM), 25 with one abnormal value at the oral glucose tolerance test (OGTT), and 65 with normal OGTT were studied after a mean of 8.5 yr from the index pregnancy. Patients with prior gestational hyperglycemia (both one abnormal value at the OGTT and GDM) showed a worse metabolic pattern than subjects with gestational normoglycemia [respectively higher values of body mass index (BMI), waist, blood pressure, serum glucose, insulin, C-peptide, homeostatic model assessment (HOMA), fibrinogen and lower levels of HDL-cholesterol]. Prevalence of the metabolic syndrome and its components was 2-4-fold higher in women with prior gestational hyperglycemia (and 10-fold higher if pre-pregnancy obesity coexisted) when compared to normoglycemic controls; in a Cox proportional hazard model, after adjustments for age and pre-pregnancy BMI, gestational hyperglycemia and pre-pregnancy BMI predicted subsequent metabolic syndrome [respectively: hazard ratio (HR)=4.26 and HR=1.21] and most of its components. In the same model, the highest quartile of fasting serum glucose at the OGTT of the index pregnancy was significantly associated to the metabolic syndrome and its components. Gestational hyperglycemia and fasting glucose values were also associated to subsequent fibrinogen values, but not to albumin excretion rates. In young adult women, prior gestational hyperglycemia (particularly abnormal fasting glucose values), above all in combination with pre-pregnancy obesity, anticipates a subsequent syndrome at high cardiovascular risk and, possibly, a mild chronic inflammatory response.

Obesity or diabetes: what is worse for the mother and for the baby?

OBJECTIVES: The aim of the present study is to evaluate pregnancy outcomes in a cohort of Caucasian pregnant women in relation to their body mass index and glucose tolerance status; the role of central fat distribution, as indicated by waist-to-hip circumference ratio, was also considered. METHODS: Seven hundred women were studied; they had gestational diabetes or impaired glucose tolerance (250) or normoglycaemia (450). Among them 117 had pre-pregnancy overweight/obesity (44 were obese), 133 hyperglycaemia, but normal weight, and 117 hyperglycaemia and overweight/obesity (42 were obese). RESULTS: Hypertension, cesarean delivery and prevalence of large-for-gestational age babies were higher in obese (both with normoglycaemia and hyperglycaemia), mainly in those with greater gestational weight gain and central fat distribution (waist-to-hip ratio > 0.90). Normal weight hyperglycaemic women showed better outcomes than obese normoglycaemic women did. In a multiple logistic regression model, obesity (OR=10.6; 95% CI 5.00-22.54) was directly related to hypertension, and independent predictors of cesarean section were: gestational hyperglycaemia (OR=1.78; 95% CI 1.21-2.62), gestational weight gain (OR=1.06; 95% CI 1.02-1.10), and central obesity (OR=1.51; 95% CI 1.02-2.24), while obesity (OR=4.48; 95% CI 2.30-8.71) gestational weight gain (OR=1.08; 95% CI 1.03-1.12) and central fat distribution (OR=1.81: 95% CI 1.12-2.93) were directly related to delivering larger babies, after multiple adjustments. CONCLUSION: These results suggest that pre-pregnancy obesity and gestational hyperglycaemia were independent risk factors for different adverse pregnancy and neonatal outcomes, while central distribution of fat, and gestational weight gain play an additive adverse role on these outcomes.

Maternal low birth weight and gestational hyperglycemia.

We aimed to investigate whether birth weight could predict the subsequent risk of gestational diabetes and impaired glucose tolerance. Consecutive women with a singleton pregnancy and gestational diabetes (n = 50), impaired glucose tolerance (n = 50) and normoglycemia (n = 200) were included in the study. Birth data were collected from original hospital records of the women. Women with gestational hyperglycemia were significantly older and heavier than those with normoglycemia. Maternal birth weights significantly declined for each class of glucose tolerance (3389 +/- 644; 3184 +/- 583 and 3077 +/- 661, respectively for women with normoglycemia, impaired glucose tolerance and gestational diabetes). After adjustment for age, gestational age and weight gain, maternal diabetes, and pre-pregnancy body mass index, maternal birth weight was negatively related to impaired glucose tolerance (OR 0.88, 95% CI 0.81-0.97) and to gestational diabetes (OR 0.82, 95% CI 0.74-0.91) in a multiple logistic regression model. These findings suggest that women with low birth weight constitute a group at increased risk for both gestational impaired glucose tolerance and diabetes.

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.

Dietary fat and gestational hyperglycaemia.

AIMS/HYPOTHESIS: The purpose of this study was to investigate the relation between life-style habits and glucose abnormalities in Caucasian women with and without conventional risk factors for gestational diabetes. METHODS: A total of 126 pregnant women with gestational diabetes, 84 with impaired glucose tolerance and 294 with normal glucose tolerance, identified by sequential screening, were interviewed to determine their usual weekly food pattern, amount of exercise, smoking habits and alcohol intake. RESULTS: Patients with glucose abnormalities were older and shorter in height and had significantly higher BMI before pregnancy, percentage of diabetic first-degree relatives and higher intake of saturated fat. Patients without known risk factors for gestational diabetes (i. e. younger than 35 years of age, BMI < 25 kg/m2, no first-degree diabetic relatives) included 40 with impaired glucose tolerance or gestational diabetes. In a multiple logistic regression model age, short stature, familial diabetes, BMI and percentages of saturated fat were associated with impaired glucose tolerance or gestational diabetes in all patients, after adjustment for gestational age. In patients without conventional risk factors only percentages of saturated fat (OR = 2.0; 95 %-CI = 1.2-3.2) and polyunsaturated fat (OR = 0.85; 95 %-CI = 0.77-0.92) were associated with gestational hyperglycaemia, after adjustment for age, gestational age and BMI. CONCLUSION/INTERPRETATION: Saturated fat has an independent role in the development of gestational glucose abnormalities. This role is more important in the absence of conventional risk factors suggesting that glucose abnormalities could be prevented during pregnancy, at least in some groups of women.

Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study.

It is still unclear whether i.v. immunoglobulins (Ig) can facilitate the reproductive prognosis of women who have suffered recurrent pregnancy loss. We report the results of a multicentre placebo-controlled study on the effect of Ig administration on pregnancy outcome in 46 women who had suffered at least three recurrent miscarriages. All were screened to exclude chromosomal or Müllerian abnormalities, the presence of antinuclear antibodies, lupus anticoagulant (LA) or elevated titres of anticardiolipin antibodies which may have revealed an underlying autoimmune problem. To avoid a selection bias towards ongoing pregnancies, i.v. Ig or placebo were administered between weeks 5 and 7 of gestation for 2 consecutive days as soon as each woman knew she was pregnant and before embryonic heart activity could be detected. A further infusion was administered at week 8 when ultrasonography confirmed an ongoing embryonic development. In all, 68% of the women who received Ig went to term versus 79% of those who received a placebo (not significant), with no significant differences in the pregnancy course or the perinatal outcome. These results suggest either that women with recurrent miscarriages who have no recognized cause of pregnancy loss have a good reproductive prognosis without any treatment or that the emotional care associated with the administration of a placebo can indirectly facilitate the progression of pregnancy.

Capillary glucose determination in the screening of gestational diabetes.

Paired capillary-venous blood samples were obtained from 418 pregnant women undergoing an oral glucose challenge test (GCT) for the screening of gestational diabetes (GD). The relationship between capillary and plasma glucose concentrations was investigated in order to establish a capillary GCT threshold. Plasma glucose was assayed by the glucose oxidase method and capillary glucose using Reflocheck Glucose strips and a Reflocheck reflectance meter. During GCT the capillary values exceeded plasma glucose values by a mean difference of 10-12 mg/dl fasting and 22-24 mg/dl after 1 h. A high correlation between the glucose values of the two techniques was found, particularly for those at 1 h, with corresponding capillary determinations being 20 mg/dl above plasma values. The sensitivity, specificity and predictive value of the various capillary thresholds investigated in detecting GD corresponded substantially to the accuracy of plasma thresholds 20 mg/dl lower. The receiver operator characteristic curves of the plasma and capillary thresholds were similar in shape and the optimal cut-off point for performing a diagnostic test was set at 135 and 155 mg/dl, respectively. These cut-off values should be reconsidered in the light of the costs and perinatal outcome.

[Diagnosis of pulmonary maturity in the fetus]. / La diagnosi della maturità polmonare nel feto.

The various biochemical and biophysical methods to assess fetal lung maturity are reviewed. So far the most widely used biochemical method is the L/S ratio, but in complicated pregnancies mainly in diabetes mellitus, the determination of the lung profile (including PG) must be carried out to reduce false immature ratios. Biophysical methods, like foam stability tests and optical density, are easy and quick, but less precise.

Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy.

Two groups of pregnant diabetic women, fifteen with type I and fourteen with type II diabetes, were randomly assigned either to CSII or to ICT and the subgroups compared with respect to glycaemic control, insulin requirement and perinatal out-come. Ten non-diabetic pregnant women served as controls for the variations in the metabolic parameters considered (24-hour mean blood glucose and glycosylated hemoglobin). Strict glycaemic control was achieved and maintained by both regimens before week 13 in all patients with type I and in 57.1% of patients with type II diabetes. The mean insulin requirements in the type I group increased up to week 34-36 and then stabilized to term in patients receiving CSII and rose progressively to term in those receiving ICT. In the type II group insulin requirements rose up to week 36 in patients receiving CSII and up to week 32 in those receiving ICT, stabilizing thereafter on both regimens. No significant differences in mean insulin requirement at the different stages of gestation were found between the patients receiving CSII and those receiving ICT of either group. Perinatal outcome was satisfactory in both groups, although control of foetal growth was better with ICT than with CSII. CSII is a practical, safe and effective method of maintaining maternal normoglycemia in pregnancy but for the present we cannot consider it superior to ICT in the treatment of pregnant diabetic women.