Pregnancies in an 18-Year Follow-up after Biliopancreatic Diversion

Background: 239 pregnancies occurred in 1136 women who had undergone biliopancreatic diversion (BPD). Methods: There were 73 abortions, and 14 pregnancies are presently in their course. The 152 term pregnancies (six twins) occurred in 129 women 2-173 months (mean 42.7) after BPD. Mean age and current excess weight were 31.4 years (20-42) and 29.1% (-6.9-78.2), and mean excess weight loss was 72.9% (30.4-110.5). Results: Mean weight gain during pregnancy was 6.2 kg (-21-25). In 32 patients (21%), parenteral nutritional support was needed. In all the other patients (79%), the usual supplementations were given. Of the newborns, 122 were delivered at term (84.7%) with a mean weight of 2842.4 g (1760-4600 g) and a mean length of 48.5 cm (43-59 cm), while the 22 preterm babies (15.3%) weighed 2151.1 g (1400-3850 g) and had a length of 44.6 cm (33-56 cm). Forty infants (27.8%) were small for gestational age but 17 of them weighed more than 2500 g. Eleven twins (one abortion at 26th week) were also delivered, with a mean weight of 2088.6 g (1200-3100 g) and a mean length of 45.6 cm (35-50 cm). Delivery was spontaneous in 85 instances (56%), while vacuum extractor was used in one, and 66 cesarean sections were performed. There were two birth malformations, one infant died after surgery for meconium obstruction and two died from unknown causes. Of the 129 women, 35 had been infertile before BPD. Conclusions: Disappearance of infertility and decrease of pregnancy risk are to be considered among the beneficial effects of weight reduction following BPD.     

Immunological changes among workers occupationally exposed to styrene

The functional status of the immune system was investigated in a group of 71 workers exposed to styrene and in 65 control subjects, recruited according to the same selection criteria and comparable as to sex, age, and confounding variables. Air and biological monitoring were used to characterize styrene exposure (median of the main urinary metabolites in the next-morning spot samples: 106 mg/g creatinine). Phenotypic analysis of peripheral blood lymphocytes (PBL) by automated flow cytometry revealed a reduced proportion of T lymphocyte subsets (CD3⁺, CD4⁺ and CD4⁺45⁺), with no changes in CD8⁺, and a higher proportion of B lymphocytes (CD19⁺) among styrene-exposed workers. The exposed workers showed a higher proportion of activation markers, namely DR and interleukin-2 receptors (CD25). Immunoglobulin subclasses were comparable in the two groups. An increased prevalence of abnormally low values was apparent for CD2⁺, CD3⁺, CD4⁺, CD4⁺45⁺ and CD11b subsets among workers exposed to styrene, whereas CD19⁺, DR⁺ and CD25⁺ showed an increased prevalence of abnormally high values. Natural killer-related phenotypes (CD56⁺, CD56+16⁺, and CD56⁺16^–) were more expressed among styrene workers, with average increase of 30%. However, the frequency distribution of the lytic activity of natural killer cells against K-562 target cells was shifted towards lower values in the exposed workers as compared to control subjects. Dose-response relationships between indices of internal dose and prevalence of abnormal values were detectable for T lymphocyte subsets, NK phenotypes, and activation markers. These findings suggest that moderate exposure to styrene is associated with an altered distribution of lymphocyte subsets. The decreased proportion of T lymphocytes, mainly of T helper-inducer cells, could hamper regulatory functions, thus suggesting a negative modulation by styrene exposure. Since a proper balance between immunocycte subsets is important for immunological responses, such changes should be regarded as adverse effects.     

Prognostic factors in fetal hydronephrosis: a multivariate analysis

With the increasing use of obstetric echography fetal hydronephrosis has been reported more frequently. The purpose of this study was to identify prognostic factors associated with adverse outcome, such as renal failure and death, in fetal hydronephrosis. One hundred and forty-eight children with fetal hydronephrosis were admitted, submitted to a systematic protocol, and prospectively followed. Prognostic factors associated with fetal echography and clinical and laboratory findings on admission were studied. The median follow-up was 39 months. The analysis was conducted in two steps. In a univariate analysis, variables associated with adverse outcome were identified by the Kaplan-Meier method. The variables that were significantly associated with adverse outcome were then included in a multivariate analysis. This analysis, using the multivariate Cox’s model, was performed to identify variables that were independently associated with a worse prognosis. Only variables that remained independently associated with adverse outcome were included in the final model. After final adjustment by Cox’s multivariate model, three variables were identified as independent predictors of adverse outcome: oligohydramnios, prematurity, and glomerular filtration rate lower than 20 ml/min. Thus, in the presence of oligohydramnios, prematurity, and abnormal renal function, the medical team must plan appropriate follow-up for infants at health centers prepared to investigate and treat uropathies in newborns. Received: 24 August 1998 / Revised: 7 December 1998 / Accepted: 11 December 1998     

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.     

Ewing's sarcoma of the bone. Anatomoclinical study of 424 cases]

The clinic-epidemiologic and prognostic features of 424 cases of Ewing sarcoma observed at "Rizzoli" Institute between 1972-1990 are reported. The incidence of the tumor was higher in the second decade of life with slight predominance in the male sex. The primary lesion was especially localized in the extremity and the ratio lower/upper extremity was 5/1. We did not find, in contrast with other Authors, differences in height or in incidence of congenital malformations when compared to controls. The pain was the first common symptom at debut (90%) followed by swelling (50%) and fever (40%). Diagnosis was made 5.5 months after the first symptom and the delay was due to wrong diagnosis at debut in 3/4 of the patients. Laboratory tests showed anemia in about half of the patients and increased value of ESR (60%) and LDH (40%). Seventy-one of the patients were metastatic at presentation, none of these patients were still living after three years. At a median follow-up of 9 years 43% of the patients with localized disease, treated with adjuvant and neo-adjuvant chemotherapy remained continuously disease free, 53% developed metastatic disease and/or local recurrences and 2% had a second malignancy. In 24% of the patients metastases and/or local recurrences appeared three years after the beginning of treatment. Better prognosis was observed in female patients, without fever at diagnosis, with tumor localized at extremities and with normal value of hemoglobin, ERS and LDH. Regarding the type of treatment, better results were obtained by surgery of the primary tumor and by chemotherapy with four drugs (vincristine, cyclophosphamide, adriamycin dactinomycin) in comparison to radiotherapy of the primary tumor and chemotherapy with three drugs (vincristine, cyclophosphamide, adriamycin).     

Limited value of zinc protoporphyrin as a marker of iron status in chronic hemodialysis patients

BACKGROUND: In an attempt to find new parameters able to evaluate the actual iron availability by bone marrow cells, zinc protoporphyrin (ZnPP), a metabolic intermediate generated in the red blood cell by the incorporation of zinc instead of iron, has been proposed. ZnPP is a good marker of iron-deficiency anemia in non-uremic people, as red blood cell ZnPP concentration rises specifically (except for lead intoxication) in this condition. Existing data on ZnPP as a marker of iron deficiency in uremic patients comes mainly from cross sectional studies on chronic hemodialysis and has produced conflicting results. SUBJECTS AND METHODS: Therefore, we prospectively studied 42 HID patients, 28-88 years old, 13-346 months of dialysis age, beginning from a period of maximal iron deficiency, due to the lack of parenteral iron compounds (T0) up to the end of more than one year of follow-up with continuous parenteral iron supplementation (T4). ZnPP, hemoglobin, transferrin saturation and ferritin were serially determined before and after six weeks (T1), four months (T2), seven months (T3) and 14 months (T4) of parenteral iron supplementation at a maintenance dose of 0.5-1 mg/kg/week. RESULTS: In comparison with baseline values (95+/-37 micromol/mol heme) there were no significant changes in ZnPP levels at T1 and T2 despite a continuous increase in both transferrin saturation and ferritin values, while ZnPP significantly decreased at T4 (63+/-37 micromol/mol heme, p<0.001). There was no correlation between ZnPP and both transferrin saturation and ferritin at any time during the study, the same was true for ZnPP and zinc and lead serum concentration, fibrinogen and reactive C protein levels at T1 and T4, respectively. At T4, only 2/10 patients who still showed ZnPP levels >80 micromol/mol heme had absolute or functional iron deficiency, when the percentage of hypochromic red cells were measured. CONCLUSION: We conclude that ZnPP untimely parallels a change in iron balance in only a proportion of uremic people, in as much as confounding factors, such as chronic inflammation and uremia in itself may obscure its relationship with iron status. Therefore, ZnPP cannot be assumed to be a first-line diagnostic marker of iron balance in uremic patients.     

Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients.

PURPOSE: Imatinib (Glivec) is a potent inhibitor of bcr/abl, an oncogenic fusion protein that causes chronic myelogenous leukemia (CML). alpha1 acid glycoprotein (AGP) binds to imatinib with high affinity and inhibits imatinib activity in vitro and in vivo in an animal model. A pharmacokinetics analysis of imatinib was undertaken in CML patients. EXPERIMENTAL DESIGN: Imatinib plasma concentrations were measured in 19 CML patients treated with imatinib (400 or 600 mg/day). Five patients received a concomitant short-term course of clindamycin (CLI). RESULTS: A positive correlation between AGP and imatinib plasma levels was observed. CLI administration decreased imatinib plasma concentrations, evaluated as area under the curve (AUC) and peak concentrations (C(max)). The effects of a bolus of CLI was studied in three patients on imatinib 23 h after the last imatinib dose. Within 5-10 min in three of three cases, CLI caused a decrease in imatinib plasma concentrations of 2.6-, 2.7-, and 4.7-fold, respectively. In vitro experiments using fresh blasts from CML patients showed that AGP, at concentrations observed in the patients, decreased imatinib intracellular concentrations up to 10 times and blocked imatinib activity. The incubation with CLI restored imatinib intracellular concentrations and biological activity. CONCLUSION: AGP exerts significant effects of the pharmacokinetics, plasma concentrations, and intracellular distribution of imatinib in CML patients; these data indicate that plasma imatinib levels represent unreliable indicators of the cellular concentrations of this molecule.     

An Analysis of Approaches to the Management of Endometrial Cancer in North America: A CTF Study

Objective.The aim of this study was to define the clinical–therapeutical approach to endometrial cancer now being followed in some of the most important centers of reference for gynecological cancer in North America by means of a questionnaire.Study design.The questionnaire focused on four principal areas: (1) surgical staging and therapy; (2) adjuvant treatment; (3) treatment modifications; and (4) management of advanced stages (FIGO III–IV).Results.There were 48 evaluable responses (77%) received by the end of December 1994 which were considered for this analysis. Lymphadenectomy is utilized routinely in 26/48 centers (54.2%) and in selective clinical–pathological conditions in another 21/48 centers (43.5%). In the majority of centers (31/48; 64.6%) radical surgery is utilized for selected indications such as cervical involvement. Only 3/48 (6.2%) centers consider the vaginal approach totally inappropriate. The great majority (40/48; 83.3%) of the centers considered postsurgical adjuvant therapy to be necessary in FIGO Stage Ic. Brachytherapy is routinely performed in 3 centers (6.2%) in postsurgical management of Stage I endometrial cancer, while the majority of the centers (31/48; 64.6%) perform brachytherapy of the vaginal vault in certain clinical–pathological conditions. A wide variety of treatments are used for advanced stages (FIGO III–IV).Conclusions.It emerges that some controversial aspects exist on endometrial cancer treatment, and these conflicting data need a large-scale multicenter randomized clinical trial.