T1 colon cancer in the era of screening: risk factors and treatment.

BACKGROUND: The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit. METHODS: The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data. A univariate and multivariate logistic regression analysis was performed to analyze the significance of each factor both in terms of lymph node (LN) harvesting and LN metastases. RESULTS: Out of 507 patients enrolled, 394 patients were considered for analysis. Thirty-five (8.91%) patients had positive LN. Statistically significant differences related to total LN harvesting were found in relation to central vessel ligation and segmental resections. Cumulative distribution demonstrated that the rate of positive LN increased starting at 12 LN harvested and reached a plateau at 25 LN. CONCLUSIONS: Some factors associated with an increase in detection of positive LN were identified. However, further studies are needed to identify more sensitive markers and avoid surgical overtreatment. There is a need to raise the minimum LN count and to use the LN count as an indicator of surgical quality.

CXCR7-mediated progression of osteosarcoma in the lungs.

BACKGROUND: Osteosarcoma (OS) is the most frequent primary malignant bone tumour in children and adolescents with a high propensity for lung metastasis. Chemokines and chemokine receptors have been described to have an important role in many malignancies including OS. The aim of this study was to investigate the expression of CXCR7 receptor in OS tissues and its role in the progression of the disease in the lungs. METHODS: Immunohistochemistry was used to study CXCR7 expression in primary tumours and metastatic tissues from patients with OS. Its contribution to tumour expansion in the lungs has been also assessed using animal models and synthetic-specific CXCR7 ligands. RESULTS: CXCR7 was expressed on human primary bone tumours and on lung metastases. Its expression was predominantly located on tumour-associated blood vessels. Mice challenged with OS cells and systematically treated with synthetic CXCR7 ligands presented a significant reduction of lung nodules compared with untreated mice. CONCLUSION: This study shows that CXCR7 has a critical role in OS progression in the lungs, where are expressed CXCR7 ligands, especially CXCL12. Moreover, we highlight that synthetic CXCR7 ligands could represent a powerful therapeutic tool to impede lung OS progression.

ACTH 1-17 effects on intermediary metabolites in healthy subjects.

Some acute and chronic metabolic effects of a new ACTH analogue (ACTH 1-17, Synchrodyn) were evaluated in healthy subjects and compared to those of the synthetic fragment ACTH 1-24. The peptides were injected at doses reportedly comparable with regard to their corticotropic effect, i.e. 100 micrograms ACTH 1-17 and 250 micrograms ACTH 1-24. A similar increase in blood glucose, NEFA and ketone bodies concentrations, without any significant modification of insulin, C-peptide and glucagon levels, was observed after injecting both peptides. The chronic treatment with ACTH 1-24 induced a significant increase in basal lactate, pyruvate and alanine blood concentrations. The levels of these metabolites resulted unaffected or slightly reduced after the corresponding treatment with ACTH 1-17. Our data are compatible with a certain degree of exhaustion of the adrenocortical reserve or, alternatively, a resetting of the circadian cortisol rhythm after prolonged treatment with the ACTH 1-17 analogue.

[Biochemical markers for bone activity and osteoporosis]. / Markers biochimici dell'attività ossea e osteoporosi.

Osteoporosis is characterized by reduced bone mass, derangement of bone microscopic architecture and increased risk of fractures. For the evaluation of this risk an important role is played by bone mass peak (measurable with mineralometric techniques) and the rate of bone resorption. The latter can be assessed by means of many laboratory indexes, taken as markers of bone cells activity. The latest markers of osteoblastic activity are osteocalcin and the terminal fragment of type I pro-collagen. On the other hand pyridinolines are considered markers of bone resorption. The authors describe the assay procedures and the clinical meaning of these markers of bone metabolism.

ACTH 1-17 effects in insulin dependent diabetes mellitus.

The aim of this study was to evaluate the metabolic effects of a new synthetic ACTH analogue (ACTH 1-17) in insulin-dependent diabetic subjects. ACTH 1-17 (100 micrograms, intramuscular injection) was administered at 07(00)-07(30) every second day for 20 days. Changes in insulin dosage were carried out to maintain the same metabolic control during the period of the study. Before and after treatment diurnal plasma glucose profiles were superimposable and insulin requirement increased only in 16 out of 19 patients (mean: 6.7 +/- 2 U/die; range: 2-22 U/die). No changes were observed in diurnal profiles of blood alanine, glycerol, total ketone bodies and plasma NEFA, C-peptide, glucagon. The physiological blood lactate and pyruvate peaks following the evening meal were initially absent and could be detected after treatment. From our data it is not clear whether the more physiological pattern of blood lactate and pyruvate is caused by the modest increase in insulin dosage or is a specific effect of the treatment.

Correlations between glycosylated haemoglobin and other metabolic parameters in insulin-dependent diabetics.

The metabolic parameters of 40 insulin-dependent patients (22 females and 18 males) have been studied to evaluate their intercorrelations. We obtained positive correlation between glycosylated haemoglobin and triglycerides (r = +0,460; p less than 0,01) and between HbA1 and mean diurnal plasma glucose (MDPG) (r = +0,652; p less than 0,001). There was a negative correlation between HbA1 and high density lipoproteins (HDL) cholesterol (r = -0,406; p less than 0,05). No significant correlation was found between HbA1 and either uric acid or total cholesterol. Correlations were also found between MDPG and triglycerides, MDPG and HDL-cholesterol, triglycides and HDL-cholesterol, uric acid and HDL-cholesterol. These correlations are discussed.

Theophylline in the treatment of the elderly with chronic obstructive pulmonary disease.

The authors describe the pharmacological effects of theophylline and elucidate its mechanisms of action according to latest hypothesis. The narrow therapeutic range of the drug and the existence of factors capable of modifying its distribution and clearance in the elderly, are taken into consideration, as well. The behaviour of theophylline concentrations in two groups of elderly subjects affected by chronic bronchitis, treated respectively with intravenous aminophylline and anhydrous theophylline administered orally are assessed. Usefulness of associating the two routes of administration is underlined. In fact, the delay in the achievement of the therapeutic range observed after oral intake can be made up for by the initial peak induced by intravenous injection. Our observations in the elderly are consistent with the necessity of therapeutic monitoring. In addition, a careful dosage of the drug can avoid the occurrence of untoward effects.

Blood lactate behavior after glucose load in diabetes mellitus.

The aim of this study was to evaluate the relationships between blood lactate and plasma glucose, insulin (IRI) and C-peptide (IRCP) during the first hour of an oral glucose load (OGTT, 100 g). Twelve controls, sixteen non-insulin-dependent (NIDDM) and four insulin-dependent (IDDM) diabetic subjects were studied. A significant increase in blood lactate was observed at 15 min in normal subjects, whereas there was a delayed increase at 45 min in NIDDM subjects, in the presence of IRCP increments of 0.31 nmol/l. In order to have a minimum significant lactate increment, the threshold value of peripheral IRCP increment was about 0.30 nmol/l. In IDDM subjects, despite considerable hyperglycemia, blood lactate concentration remained unchanged throughout the test. In normal and NIDDM subjects there was a significant negative correlation between delta lactate and delta glucose (r = -0.89, p less than 0.001) and a significant positive correlation between delta lactate and delta IRCP (r = 0.78, p less than 0.001). In conclusion, hyperglycemia itself and the lack of increase in insulin secretion do not affect blood lactate increase during OGTT; blood concentration of this metabolite depends mainly on an early insulin secretion apt to enhance tissue glucose uptake and to inhibit gluconeogenesis.

[Multiple symmetrical lipomatosis. Metabolic effects of excision of lipomatous tissue]. / Lipomatosi multipla simmetrica. Effetti metabolici dell'exeresi di tessuto lipomatoso.

Multiple Symmetric Lipomatosis (MSL) is a syndrome characterized by the occurrence of symmetric lipomas over various regions of the body. No clear etiology has been recognized while a frequent association with systemic metabolic abnormalities has been described. The metabolic situation of a subject affected by MSL was assessed before and after surgical excision of lipomas. A condition of impaired glucose tolerance (IGT) was verified both before and after surgery by the performance of oral glucose tolerance test, glucagon test, and daily glucose profile. No significant differences were observed after the ablation of lipomatous masses with regard to glucose, IRI, IRCP and NEFA behaviour. We concluded that the resection of lipomas can not modify glucose tolerance in MSL and that lipomas can be considered as tissues metabolically independent from the rest of body fat.