Prognostic value of metastatic pattern in colorectal cancer: a multicenter retrospective analysis in a real-life cohort.

BACKGROUND: Metastatic patterns have been linked with prognosis in colorectal cancer. We aim to determine the distribution of metastases, their dynamics during disease and their prognostic impact for specific clinical treatment scenarios (resection of metastasis and/or systemic treatment, best supportive care). MATERIAL AND METHODS: 978 patients diagnosed with metastatic colorectal adenocarcinoma treated at three oncological centers from 2006 to 2018 were included. Overall survival was assessed depending on tumor load, distribution of metastases and treatment of the patients. RESULTS: Most patients had single site metastasis (n = 684; 69.9%): 398 patients had liver (n = 398; 40.7%) and 103 patients had lung only metastasis (10.6%). The number of organs involved in metastases at diagnosis was highly prognostic (HR 0.77; CI 0.65, 0.90), whereas the additional gain of metastases during progression of the disease was not. The majority of patients (62.9-74.2%) with initial lung, liver or both metastases retained their initial metastatic status. In the overall population, lung only metastases were associated with the most favorable outcome (HR 0.64; CI 0.50, 0.81). This was also observed in patients receiving best supportive care (HR 0.45; CI 0.27, 0.75). Resection of lung only metastases resulted in longer median survival (102.2 months). A relevant survival difference in patients treated by systemic therapy alone was not observed. Lung only metastasis was associated with rectal cancer (p < .001) and RAS-mutation (p = .01); both, lung and liver metastasis were associated with time from diagnosis to first metastasis (p < .001). CONCLUSION: The number of organs involved in metastasis at diagnosis but not the total cumulative number of involved organs is of prognostic relevance in colorectal adenocarcinoma. This prognostic relevant initial metastasis distribution remains unchanged in the majority of patients during the disease. However, the prognostic impact of the metastatic pattern is potentially altered by treatment modality.

Transferrin receptor in serum. A new tool in the diagnosis and prevention of iron deficiency in blood donors.

BACKGROUND: Transferrin receptor mediates cellular uptake of iron, and the expression on cells reflects iron needs and erythropoietic activity. The results of measuring transferrin receptor in serum (sTfR) in blood donors are presented. STUDY DESIGN AND METHODS: Haemoglobin, serum-ferritin and sTfR were measured in 172 female and 174 male donors that had donated whole blood six or more times during the previous 3 years and in 96 female and 56 male new donors. RESULTS: Haemoglobin and sTfR were not significant different in new and repeat donors. New donors had significantly higher s-ferritin than repeat donors. Twenty donors had a Hb above the low limit for normal, but below the determined cut-off for donation. Only three of these had high sTfR and/or low serum-ferritin. Hence, of the total 492 donors 3.5% were below the Hb cut-off, but having Hb, s-ferritin and sTfR within normal ranges. 11.6% of new female donors belonged in this category. CONCLUSION: STfR is better than s-ferritin as a screening for iron deficiency. Most donors with low tissue iron neither have high sTfR, nor anaemia. There is probably no need to have a separate, higher than the lower normal range, requirement for Hb in donors. STfR measurements are probably most valuable in a setting where most donors are repeat donors.

Magnesium status in healthy free-living elderly Norwegians.

OBJECTIVE: Magnesium (Mg) status has previously not been properly assessed among healthy elderly subjects. METHODS: Thirty-six healthy elderly subjects participated. Their Mg status was assessed by serum Mg, basal urinary Mg output, and with a Mg loading test (30 mmol infused during 8 hours; urine sampled 24 hours), and compared with 53 healthy younger subjects. Their dietary intake was assessed by a quantified food frequency questionnaire. Fourteen of the subjects received 300 mmol Mg to study the effect on Mg status. RESULTS: With the exception of vitamin D in women, average energy and nutrient intakes were adequate. All subjects had serum Mg levels within the reference value of the laboratory. Basal urinary Mg excretion was 3.3 +/- 1.1 mmol/day and 24-hour Mg retention after a Mg load was 28 +/- 16% compared to 6 +/- 11% in younger controls, suggesting Mg deficiency in the elderly. In the 14 subjects who received oral Mg supplementation there was a statistically significant increase in basal urinary Mg excretion and creatinine clearance, and decreases in Mg retention, serum Mg and serum creatinine. CONCLUSIONS: This study suggests that a significant subclinical Mg deficit, not detected by serum Mg, was present in many of these healthy elderly subjects. Mg supplementation improved Mg status and renal function.

Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics.

Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics.

Magnesium deficiency diagnosed by an intravenous loading test.

Magnesium deficiency is common but difficult to diagnose and to assess in clinical practice. The use of a magnesium loading test was therefore evaluated to diagnose magnesium deficiency in 661 hospitalized patients with medical conditions assumed to interfere with magnesium uptake and excretion. Thirty millimoles of magnesium sulphate were administered intravenously during 8 h as a loading test and related to the urinary excretion in the following 24 h. A group of 30 patients without any known predisposition for magnesium deficiency and a group of 27 healthy volunteers served as controls. The mean (with 95% confidence interval) magnesium retention was 4 (-2-10)% in the control group of patients and 3 (-2-8)% in healthy subjects. A significantly higher retention was observed in all the groups of the patients: atrial fibrillation 18 (11-25)%, other arrhythmias 18 (11-24)%, hypertension 27 (20-33)%, coronary artery disease 25 (20-30)%, congestive heart failure 31 (26-37)%, cerebrovascular events 38 (24-51)%, gastrointestinal disorders 22 (14-29)%, diabetes mellitus 16 (9-22)%, and alcoholics 33 (29-36)%. The percentage of patients with a retention greater than mean + 2 SD of the two control groups varied between 22% and 54% among the different patient groups. The mean serum magnesium among the patient groups was similar to the control group of patients, except for the alcoholics, hypertensives and young healthy controls, who had significantly reduced levels. Magnesium retention was significantly correlated to age and renal function, and among the alcoholics negatively correlated to serum magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral versus intravenous magnesium supplementation in patients with magnesium deficiency.

The efficacy of oral magnesium supplementation in correcting magnesium deficiency was examined in a group of 40 elderly patients with suspected magnesium deficiency. The patients were randomized in a double-blind, placebo-controlled fashion to oral magnesium-lactate-citrate for 6 weeks. Magnesium status was assessed by an intravenous magnesium-loading test at baseline and after treatment. For comparison, another group of 23 patients received 30 mmol magnesium sulfate intravenously daily for 7 days. A group of 30 patients without known predisposition to magnesium deficiency and a group of 27 young healthy subjects served as controls. The initial magnesium-loading test in the placebo group reduced magnesium retention from a mean 41% (95% confidence intervals 34-49) to 22% (15-29) (p less than 0.01). In the group receiving oral magnesium supplementation for 6 weeks, magnesium retention decreased from 39% (31-47) to 10% (2-18) (p less than 0.01), which was significantly better than with placebo treatment (p less than 0.01). The magnesium retention after oral magnesium supplementation was comparable to that observed after parenteral administration of magnesium for 7 days, 6% (-4 to 16), and to that in the reference groups of patients 4% (-2 to 10) and healthy control subjects 3% (-2 to 8). The study suggests that the bioavailability of orally given magnesium-lactate-citrate is satisfactory, and that oral administration of magnesium for 6 weeks may restore magnesium depots in patients with magnesium deficiency.

The thyroid function in young men during prolonged exercise and the effect of energy and sleep deprivation.

Thyroid function has been investigated in 24 young military cadets participating in a 5 d ranger training course with heavy physical exercise, calorie deficiency and deprivation of sleep. The cadets were divided into three groups, each differing in the amount of sleep and food consumption. The serum levels of thyroid hormones (T4, FT4, T3, rT3) and TBG showed a biphasic pattern during the course. Initially there was an increased secretion concomitant with an increased deiodination of T4 to T3 and rT3 mainly due to physical exercise. When the activities lasted for several days without sufficient food supply the thyroid secretion decreased simultaneously with an alteration of the peripheral conversion of T4 to rT3 instead of T3. A significant correlation was found between the changes in total and free thyroxine (r = 0.9) and between the increase in rT3 and decrease in T3 (r = 0.6). TSH decreased during the first day of activities and remained low throughout the course. The TSH response to TRH stimulation was greatly reduced during the course due to physical exercise and calorie deficiency. The present investigation demonstrates that the thyroid function is strongly affected by prolonged physical exercise and a negative energy balance, whereas sleep deprivation does not have any significant influence. The results indicate that the alteration observed is not regulated just by the hypothalamo-pituitary-thyroid-axis alone.

The effect of spironolactone on lipid, glucose and uric acid levels in blood during long-term administration to hypertensives.

Spironolactone, an aldosterone antagonist, was given in a daily dose of 100 mg to 15 patients with primary hypertension for one year. Fasting levels of lipids, uric acid, glucose, insulin, potassium and growth hormone were measured before and after 6 and 12 months of treatment. Total cholesterol, LDL cholesterol, glucose, potassium and growth hormone were unchanged, HDL cholesterol fell from (mean +/- SD) 1.5 +/- 0.6 to 1.1 +/- 0.3 mmol/l (p less than 0.05) after 6 months of treatment and remained lowered (1.0 +/- 0.3 mmol/l) (p less than 0.01) after 12 months of treatment. There was a transient fall after 6 months of treatment in triglycerides from 2.4 +/- 1.5 to 2.0 +/- 1.1 mmol/l (p less than 0.05), uric acid from 380 +/- 73 to 342 +/- 58 mumol/l (p less than 0.05) and an increase in insulin from 16 +/- 9.5 to 28.6 +/- 26.8 mU/l (p less than 0.05). The blood glucose curves above fasting levels after glucose loading were unchanged during spironolactone treatment, whereas the area under the net insulin curve was higher after 6 months of treatment (163 +/- 103 mU X h/l) than before treatment (105 +/- 71 mU X h/l), indicating a small and transient insulin resistance. Thus, spironolactone impaired the glucose tolerance transiently and gave small and almost transient changes in fasting serum lipid and uric acid levels.

Clinical chemical analyses of serum obtained from capillary versus venous blood, using Microtainers and Vacutainers.

The concentrations of sixteen chemical constituents determined in specimens from skin puncture serum (capillary serum) collected in Microtainer were compared to the concentrations in venous serum collected in Vacutainer from adult individuals. Compared to venous serum, the concentrations in skin puncture serum were higher for potassium (2.9%), chloride (2.3%) and thyroid stimulating hormone (TSH) (86.7%) and lower for sodium (1.6%), calcium (3.2%), phosphorus (5.0%), creatinine (6.6%) and total protein (4.7%), whereas no differences were observed for urea, bilirubin, ASAT, ALAT, LD, insulin and thyroxin. The differences for sodium, calcium and TSH are explained by interference form the sampling device (Microtainer). Except for TSH, the differences are small and probably of minor clinical importance.

The influence of dihydralazine and angiotensin-II blockade on renal extraction of [131I]hippuran.

The renal extraction of [131I]ortho-iodohippuran ([131I]OIH) was measured during the first minutes after the bolus injection during renal vein catheterization of two groups of hypertensive patients. Concomitantly the hippuran clearance (effective renal plasma flow (ERPF) was determined with a quantitative renographic technique based on net kidney uptake between 1 1/2 and 2 1/2 min and plasma radioactivity 2 min after the bolus injection of hippuran. The study was repeated 30 min after intravenous administration of dihydralazine (0.1 mg/kg body weight) in 14 subjects (group A) and during continuous infusion of the angiotensin II blocking agent Saralasin (5 micrograms/kg . min) in 10 subjects (group B). Before dihydralazine was given, the rate of [131I]OIH extraction was (Mean +/- S.D.) 74.0 +/- 16.7% in the 2 min sample after bolus injection of hippuran, 67.5 +/- 17.3% after 10 min, falling to 53.0 +/- 15.3% after 30 min. There was no difference after dihydralazine administration, as the extraction values were 75.6 +/- 17.5 and 65.6 +/- 21.4% 2 and 10 min after the bolus injection of hippuran. The extraction values before Saralasin infusion were 74.2 +/- 15.7%, 59.8 +/- 18.2% and 47.1 +/- 16.6% at 2, 10 and 25 min after bolus injection of hippuran. Saralasin elicited no change in the extraction, as the values were 74.1 +/- 18.6% and 64.3 +/- 23.2%, 2 and 10 min after hippuran injection. For kidneys with ERPF above 100 ml/min . 1.73 m2 the extraction 2 min after hippuran injection was at the level of 82%, whereas the extraction fell rapidly with further reduction in ERPF. It is concluded that ERPF determined with the renographic technique, reflects the renal plasma flow when the clearance for the individual kidney exceeds 100 ml/min . 1.73 m2. This is the case also after dihydralazine and Saralasin administration.

Haemodynamic effects of treatment and withdrawal of spironolactone in essential hypertension.

The effect of spironolactone (50 mg b.i.d.) in essential hypertension was studied by measurement of effective renal plasma flow (ERPF), blood urea nitrogen (Ur+), serum creatinine (Cr), cardiac index (CI), plasma volume (PV), body weight (BW), mean arterial blood pressure (MAP), total peripheral resistance index (TPRI), plasma renin activity (PRA) and plasma aldosterone (PA) in two groups of patients. Ten cases had determinations before, after 5 weeks and 4 months of treatment; fourteen cases who had been treated at an average of 18 months, had measurements while on treatment and 5 weeks after cessation of the drug. Among the ten patients ERPF fell in six and increased in four patients during treatment, but was statistically unchanged in the total group. Ur + and Cr were also unchanged by treatment. ERPF was unchanged after withdrawal of the drug. During treatment BW decreased 3.5%, PV decreased in nine and increased in one patient, while PRA and PA increased 426% and 202%, respectively. After cessation of the aldosterone blockade, BW increased 1.9%, PV 10.5% while PRA and PA fell 60% and 48.9%, respectively. MAP fell in eight out of ten patients during treatment. This fall was associated with a fall in CI or TPRI, or both. After withdrawal of the drug, MAP increased in nine and decreased in five of the patients. The data shows that this dosage of spironolactone gave minor adjustments of the systemic and renal circulation in spite of the consistent changes in BW, PV, PRA and PA.

Pulmonary blood volume and interventricular circulation time in physically trained and untrained subjects.

Resting pulmonary plasma and blood volumes (PPV and PBV), interventricular circulation time (IVCT), cardiac and stroke index (CI and SI), heart rate (HR), total plasma and blood volumes (PV and BV) were determined in athletes (two male groups representing different types of sport activities, and one female group) and compared with those of non-athletes (one male and one female group). In addition to high maximal aerobic power, the athletes were characterized by greater SI, BV and PV and lower resting HR than non-athletes, PPV and PBV were significantly larger and IVCT significantly longer in the trained than in the untrained groups, probably reflecting an improved capacity of the pulmonary circulation. PPV as per cent of PV was almost equal in all the groups, indicating the same distribution of plasma between the pulmonary and systemic circulation. The data also indicate that total blood volume is an important determinant of the magnitude of the pulmonary vascular bed. The increased volume of flowing blood and increased stroke volume in athletes probably allows for a reduction in flow velocity and thereby a reduction in kinetic energy.