Use of serum markers in the diagnosis and management of laryngeal cancer.

Many neoplastic diseases are reported to be accompanied by the presence or associated with an increase in biological substances identified as tumour markers. The most common markers implicated in head and neck cancers are CEA, TPA, LASA, SCC, CA 19-9, and ferritin. These markers (except SCC) were evaluated in 50 patients with a laryngeal carcinoma, in 20 patients with benign lesions, and in 20 healthy subjects. The results show for each marker assayed the following sensitivity values (true positives): CEA, 10%; CA 19-9, 30%; TPA, 30%; LASA, 90%; ferritin, 60%. Specificity (true negatives) was as follows: CEA, 85%; CA 19-9, 99.4%; TPA, 98%; LASA, 99.8%; ferritin, 97%. LASA and ferritin seem to be the most suitable markers for patient monitoring because of their higher sensitivity in all phases of cancer disease.

Serum procollagen-III-peptide level correlates with disease activity in myelofibrosis with myeloid metaplasia.

In 78 patients with myelofibrosis with myeloid metaplasia (MMM) the serum procollagen III peptide activity (s-PIIIP) had a higher mean value than in 22 normal adult volunteers (22.5 v. 10 ng/ml). Nevertheless, 21.8% of the patients had s-PIIIP within the 95th percentile of the normal control group (16 ng/ml): with respect to those whose concentrations exceeded this limit, patients with normal s-PIIIP levels were younger (55.8 v. 61.2 years), had a higher Hb value (12.3 v. 10.5 g/l), a lower serum ferritin level (106 v. 464 micrograms/l) and a higher platelet count (390 v. 216 x 10(9)/l). In the overall patient population, s-PIIIP was significantly higher in those with symptoms of active disease (fever, sweating, weight loss) than in subjects with non-active disease (28 v. 16.9 ng/ml). At univariate analysis s-PIIIP correlated (at the 5% level) with increasing WBC, serum ferritin and number of transfusions and with decreasing Hb and platelet count. At multivariate analysis increasing WBC, serum ferritin and age proved to be independently associated with s-PIIIP. No relationship was found between the s-PIIIP level and morphometric grading of bone marrow fibrosis, megakaryocyte number, or lymphoid infiltration. Longitudinal studies showed that s-PIIIP increased with disease progression. The conclusion of the study is that s-PIIIP correlates more with overall disease activity than with the extent of bone marrow fibrosis.

Body iron status in critically ill patients: significance of serum ferritin.

Serial measurements of blood haemoglobin, serum iron, serum transferrin, total iron-binding capacity, transferrin per cent saturation and serum ferritin were determined in 51 post-operative critically ill patients to investigate body iron status in severely stressed patients. The results showed decreased blood haemoglobin, serum iron, serum transferrin and transferrin saturation compared to an increase in serum ferritin levels. These results indicate that there is inadequate availability of iron to tissues (secondary to rearrangement of body iron to the advantage of the iron storage compartment), which is often present in severely critically ill patients. A positive correlation was found between the initial (ferritin) levels and SAPS (r = 0.41, p less than 0.01). In addition, the increase of ferritin concentration parallels a worsening of the clinical status in severely ill patients. This is due to enhanced release by the macrophage system. From this, we consider serum ferritin as an acute-phase protein and a useful marker of the severity of the clinical status. It appears to be useful in predicting the patient's outcome, but is not reliable in evaluating iron stores in stressed patients.

Iron status in children undergoing tonsillectomy and its short-term modification following surgery.

Red cell and iron status parameters were studied in a group of 44 children undergoing tonsillectomy for recurrent throat infections and in a control group of 40 healthy children. In the patient group, before tonsillectomy, 8 children presented a latent iron deficiency and 15 a decrease in serum ferritin levels. This altered iron status can be attributed to a reduced intestinal iron absorption, due to recurrent infections. One and seven days following surgery there was a significant fall in serum iron, serum transferrin and transferrin saturation, in parallel with an increase of serum ferritin and alpha-2 globulins levels. These modifications cannot be attributed to the blood loss, as proven by the constancy of haemoglobin level and of other red cell parameters, but to an unspecific reaction to surgical stress, as observed in fever, traumas and inflammation. They reflect an altered processing of iron, with a temporary block of its release to plasma and an increased storage within the reticuloendothelial cells.

Serum thymidine kinase and beta-2 microglobulin in monoclonal gammopathies.

We evaluated the serum thymidine kinase (TK) and beta-2 microglobulin (beta-2) levels of 22 patients with monoclonal gammopathy of undetermined significance (MGUS) and of 29 patients with multiple myeloma (MM). Both parameters were significantly lower in MGUS than in MM patients and in early (stage I + II) than in advanced (stage III) MM. TK was also lower in MGUS than in stage I MM (p less than 0.025). A seven-fold increase of TK level was documented in one patient who developed a full blown picture of MM 6 years after a diagnosis of MGUS. In 3 patients with stage III MM, a sharp decrease in TK (40-77%) and in beta-2 (29-53%) levels at remission was evident with respect to the levels measured at diagnosis. Patients with high levels of TK or beta-2 had a shorter survival than those with low levels; however, this was statistically significant only for beta-2 levels (p less than 0.02). Serum TK as well as beta-2 levels appear to be of clinical value in monoclonal gammopathies and related to the course of the disease.

Increased whole body hematocrit: venous hematocrit ratio in diabetes mellitus, evidence of microcirculatory hemoconcentration.

Plasma volume and red cell volume were measured in 24 diabetic outpatients. From the blood volume measurements, the whole body hematocrit was derived, and the ratio between whole body hematocrit:venous hematocrit (WBH:VH ratio) was considered to represent an index of the difference in red cell distribution between small and large blood vessels. The WBH:VH ratio was increased in 9 out of 13 males and in 1 out of 11 females, being inversely correlated to the plasma volume (r = -0.51, p less than 0.001). Although the significance of these findings is far from clear, the occurrence of small vessel hemoconcentration in male patients with diabetes mellitus may be relevant to the pathophysiology of vascular complications of diabetes.

Polycythaemia following splenectomy in myelofibrosis with myeloid metaplasia. A reorganization of erythropoiesis.

3 patients with myelofibrosis with myeloid metaplasia were splenectomized because of anaemia and disturbing splenomegaly. In the course of the 6 months following splenectomy, a polycythaemia developed. Erythrokinetic studies demonstrated that in all cases a reduction in plasma volume and an increase in red cell volume was obtained. Total erythropoiesis decreased along with normalization of ineffective erythropoiesis and peripheral haemolysis. The reappearance of an erythropoietic activity measured over the sacrum was a constant finding, while in 1 patient, a depression of activity over the liver was observed. The new distribution and organization of erythropoiesis in the splenectomized patients is hypothesized as being due to the removal of the influence of an enlarged spleen on erythropoietic organs.

Competing models for the analysis of red cell survival obtained with 51Cr labelling technique.

A computer program for the analysis of 51Cr labelled red cell survival data was used in 84 patients and 8 normal subjects to estimate the parameters of 7 competing models derived from different hypotheses of the red cell destruction process. The purpose was to establish the optimal complexity of a red cell survival model to be used. Senescence or random destruction were the most common identified patterns of red cell death (79% of the cases). Models assuming different levels of death probability according to the age of cells, or 2 populations of cells with different death probabilities, were selected in 21% of the cases. These latter patients were characterized by the lowest values of MRCL. The conclusion of the work was that an automatic procedure for selecting the best model of red cell destruction is necessary when information concerning the mechanism of red cell death is required. For the more practical aim of obtaining an accurate measurement of the MRCL, the minimal set of competing models should account of at least 2 different populations of cells in addition to the random or senescence destruction models.

Red cell aplasia in myelofibrosis with myeloid metaplasia. A distinct functional and clinical entity.

Three patients with myelofibrosis with myeloid metaplasia are described. All three presented with grave anemia and red cell aplasia. Erythroid failure was the functional characteristic of erythropoiesis as resulted from erythrokinetic studies. Bone marrow was hypercellular or normocellular with hyperplasia of granuloblasts and megakaryocytes. Despite absent or mild splenomegaly at diagnosis, massive splenomegaly associated with a leukoerythroblastic blood film developed during the course of the disease. A relative young age (42-47 years), a subacute course of the disease and terminal blast crisis in two of them were the prominent clinical features of the patients. The differentiation from acute or malignant myelofibrosis is discussed. The patients appear to be a distinct subset within myelofibrosis with myeloid metaplasia.

Iron loading in congenital dyserythropoietic anaemias and congenital sideroblastic anaemias.

The relationship between body iron status, degree of anaemia, erythroid expansion, age and sex has been studied in eight patients with congenital dyserythropoietic anaemia (CDA) and two patients with congenital sideroblastic anaemia, who had received no or very few blood transfusions and no medicinal iron during the course of their illness. All patients had increased iron stores. Iron load was mild in three women in the reproductive age and severe in two men, in middle age, who had evidence of parenchymal organ dysfunction. Iron loading, as judged by the plasma ferritin concentration, was independent of the degree of anaemia while it was closely related to the patient's age and the degree of increase in the total erythropoietic activity. It is concluded that patients with CDA or congenital sideroblastic anaemia are at high risk of developing haemochromatosis in middle age. Prophylactic phlebotomy or iron chelation therapy should be considered for such patients.

Erythropoiesis in hairy cell leukaemia: a true erythroid failure.

A quantitative evaluation of erythropoiesis was carried out in 12 patients with hairy cell leukaemia (HCL). The results were compared with those obtained in eight patients with aplastic anaemia (AA) in order to define the characteristics of erythroid failure in HCL. Discriminant analysis was applied to both haematological and erythrokinetic parameters of the two disease groups. Plasma iron concentration and MCV were significantly higher in AA, and allowed a perfect separation of the patients. As regards erythrokinetics, values of ineffective erythropoiesis and peripheral haemolysis were able to separate completely the two disease groups, being significantly lower in HCL than in AA. A true erythroid failure was the peculiar erythrokinetic pattern of HCL. This conclusion allows one to speculate on the nature of the stem cell damage in this disease.