Fetal growth patterns in Beckwith-Wiedemann syndrome.

We provide data on fetal growth pattern on the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age-corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases.

Whole-body MRI with diffusion-weighted imaging: a valuable alternative to contrast-enhanced CT for initial staging of aggressive lymphoma.

AIM: To compare the accuracy of whole-body magnetic resonance imaging (Wb-MRI) with diffusion-weighted imaging (DWI) to that of contrast-enhanced computed tomography (CE-CT) and 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography co-registered with low dose-CT (PET-CT) in defining lymphoma disease stage. MATERIALS AND METHODS: From February 2010 to May 2014, 41 lymphoma patients underwent Wb-MRI-DWI, CE-CT, and (18)F-FDG PET-CT. Histological subtypes included aggressive B-cell (n=11), follicular (n=13), mantle cell (n=3), and Hodgkin's (n=14) lymphoma. To compare the procedures, the reference standard (RS) assessment was defined by combining the results from (18)F-FDG PET-CT, CE-CT, and bone marrow (BM) histology, modifications after therapy, and histological re-assessments of uncertain lesions. RESULTS: Among 1025 nodal sites, 217 had disease involvement according to the RS. CE-CT yielded 23 false-negative and 11 false-positive errors. Wb-MRI-DWI failed to recognise 17 localisations and had six false-positive errors; (18)F-FDG PET-CT had no errors. Among 458 extranodal sites, 37 were positive according to the RS. (18)F-FDG PET-CT yielded four false-negative and two false-positive results. CE-CT yielded 17 false-negative errors. Wb-MRI-DWI yielded a single false-negative error. Wb-MRI-DWI was the most reliable imaging technique for BM evaluation. Considering each procedure alone, the final stage would have been missed in four cases using (18)F-FDG PET-CT, 12 cases using CE-CT, and none using Wb-MRI-DWI. CONCLUSION: The present data support Wb-MRI-DWI as a sensitive and specific imaging technique for lymphoma evaluation, supporting its use in place of CE-CT for staging.

[Relationship of P 50 in normal subjects in physiological condition and their percentage of Hb-CO]. / Relazione tra P50 e percentuale di Hb-CO in soggetti normali ed in condizioni fisiologiche.

After a short review on the actual knowledge about the relationship between P50 of human blood in normal adults and newborns and their relative amount of Hb-CO, the Authors analyze a wide series of subjects in Whom the survey has been performed at the physiological saturations of Hb-CO. The results show that, a part from an usually high percentage of Hb-CO of still unknown origin in the newborn, the P50 of normal adults and newborns appear to be relatively stable and not shifted towards the right in spite of the progressive increasing of hypoxia induced by still physiological levels of Hb-CO.

22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus Arteriosus Type 2 and Review.

22q11.2 deletion syndrome is mainly characterized by conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial appearance. The etiology in the majority of patients is a 3-Mb recurrent deletion in region 22q11.2. Nevertheless, recently some cases of infrequent deletions with various sizes have been reported with a different phenotype. We report on a patient with congenital heart disease (truncus arteriosus type 2) in whom a de novo 1.3-Mb 22q11.2 deletion was detected by array comparative genomic hybridization. The deletion described corresponds to an atypical and distal deletion which spans low copy repeat (LCR) 4 and is associated with breakpoint sites that do not correspond to known LCRs of 22q11.2. We examine the clinical phenotype of our case and compare our findings with those published in the literature. The most prevalent clinical features in this type of deletion are a history of prematurity, pre-natal and post-natal growth retardation, slight facial dysmorphic features, microcephaly and developmental delay, with a speech defect in particular. These are clearly different from those found in the classic 22q11.2 deletion syndrome, and we believe that the main differential diagnosis should be with Silver-Russel syndrome. In our case we observe the cardiac phenotype with truncus arteriosus communis usually seen in the classic 22q11.2 deletion syndrome, and so far associated with the TBX1 gene. Significantly, however, TBX1 is not included in our patient's deletion. The possible roles of a position effect or other genes are discussed.

Prognostic significance of serum albumin in chronic lymphocytic leukemia.

BACKGROUND: Low levels of serum albumin have been reported to be associated with a poor prognosis in lymphoproliferative disorders. METHODS AND RESULTS: Clinical and laboratory data were retrospectively evaluated in a series of 342 patients with chronic lymphocytic leukemia (CLL). In univariate analysis, survival was significantly influenced (p less than 0.01) by traditional prognostic factors: number of lymphoid areas involved, volume of adenopathies, presence and degree of hepatomegaly and splenomegaly, anemia, thrombocytopenia, peripheral blood lymphocytosis (greater than 60 x 10(9)/l), percentage of bone marrow lymphocytes (greater than 50%). Among variables not included in the traditional staging systems, age over 70, hypoproteinemia (less than 6 gr/dl) and hypoalbuminemia (less than 3.5 gr/dl) adversely affected prognosis. All the most widely adopted staging systems recognize no more than three groups of patients with statistically different outcomes. In multivariate analysis, the prognostic value of serum albumin was independent of both age and the group of variables included in each staging system considered. CONCLUSIONS: We suggest that evaluation of the serum albumin level could be useful, in future multicenter studies, for further implementation of the staging of CLL.

[Behavior of lipoprotein X (LP-X) in viral hepatitis]. / Comportamento della lipoproteina X (LP-X) nelle epatiti virali

The AA. have studied the behaviour of LP-X in fifty cases of viral hepatitis printing out a positivity in 32% of the examined cases, with a positivity of the Au-antigen in the 34% of cases. They have observed a more remarkable inclination to the cholostasis in children (40% of the cases of positivity of LP-X), concluding for a scarce specificity of such a "marker" of cholostasis.

Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinoma.

BACKGROUND: Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive illness. Here we report long-term results of high-dose chemotherapy (HDC) as late intensification, with autologous peripheral blood stem cell (PBSC) support. METHODS: Six patients (5 men, 1 woman; median age 41years; median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone metastasis, 2) have been enrolled. All patients had been previously treated with neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a re-irradiation. Every patient received three courses of cisplatin + epirubicin and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 x 10(6)/kg (range, 4.5-18) CD34+ cells were reinfused. HDC was according ICE scheme: ifosfamide, 2.5 g/m(2)/d, + carboplatin, 300 mg/m(2)/d, + VP-16, 300 mg/m(2)/d days 1 through 4. RESULTS: After conventional chemotherapy, we had 1 CR (16%), 3 PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%),1 PR (17%), and 1 MR (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14-50), two patients are alive without disease (34%), one is alive with bone disease (16%), and three (50%) died of disease at 16, 18, and 24 months. CONCLUSIONS: HDC has an acceptable toxicity, can convert PR in CR, and seems effective, with long-lasting CRs.

Combined modality treatment with a weekly brief chemotherapy (ACOP-B) followed by locoregional radiotherapy in localized-stage intermediate- to high-grade non-Hodgkin's lymphoma.

BACKGROUND: A cooperative study was undertaken to evaluate the efficacy and toxicity of a very brief course of chemotherapy followed by locoregional radiotherapy in patients with localized-stage intermediate- to high-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHOD: From January 1988 to November 1994, 84 patients with localized stages IA and IIA intermediate- to high-grade NHL underwent a combined modality treatment. All patients underwent a six-week chemotherapy regimen, ACOP-B (doxorubicin 50 mg/sqm and cyclophosphamide 350 mg/sqm on weeks 1, 3, 5; vincristine 1.4 mg/sqm and bleomycin 10 mg/sqm on weeks 2, 4, 6; prednisone 50 mg p.o. daily throughout the first two weeks and thereafter every other day), followed by locoregional radiotherapy (36 Gy). RESULTS: The median age was 58 years, with 35% older than 65 years; 52 patients had stage I and 32 stage II; 39 patients had extranodal +/- nodal involvement, and 4 had testicular involvement. Treatment was well tolerated, with only 38% suffering from mild mucositis and no toxic deaths. Seventy-nine patients achieved CR after ACOP-B and 83 at the end of the program. With a median follow-up of four years, relapse-free survival was 79% with 15 relapses (93% disseminated). Two patients with testis lymphoma had CNS relapses. Overall survival was 90% at four years. CONCLUSION: This combined program is effective and probably curative in localized stage intermediate- to high-grade NHL, with low toxicity, also in elderly people. Patients with NHL of the testis, as primary site, require CNS prophylaxis due to the high likelihood of CNS relapse.