Three-year follow-up of 62 cirrhotic patients with hepatocellular carcinoma treated with chemoembolization

BACKGROUND: The aim of this study is to present our experience in 62 patients suffering from hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) in two years. METHODS: TACE was performed with injection of doxorubicin mixed with lipiodol before embolization with spongostan. This procedure was repeated for 3 cycles almost. Follow-up was performed by US and CT and by assessment of clinical status and biochemical tests. TACE results were assessed comparing size, local spread and TACE technique with patients' survival. The lesion was single in 51 while multiple in 11. In 6 patients the lesion was greater than 5 cm while in 56 less than 5 cm. RESULTS: Overall survival rates were 95.7% at 6 months, 78.3% at 1 year, 46% at 2 years, 40% at 3 years. The best responses were obtained with single lesions smaller than 5 cm and treated with at least 3 cycles of TACE. CONCLUSIONS: We can conclude that TACE is an efficacious therapeutic choice in the HCC patients who cannot undergo surgery.     

Bendamustine therapy in patients with relapsed or refractory Waldenström's macroglobulinemia

We report the treatment outcome for 30 relapsed/refractory Waldenström's macroglobulinemia (WM) patients following bendamustine-containing therapy. Treatment consisted of bendamustine (90 mg/m² I.V. on days 1, 2) and rituximab (375 mg/m² I.V. on either day 1 or 2) for 24 patients. Six rituximab-intolerant patients received bendamustine alone (n = 4) or with ofatumumab (1000 mg I.V. on day 1; n = 2). Each cycle was 4 weeks, and median number of treatment cycles was 5. At best response, median serum IgM declined from 3980 to 698 mg/dL (P < .0001), and hematocrit rose from 31.9% to 36.6% (P = .0002). Overall response rate was 83.3%, with 5 VGPR and 20 PR. The median estimated progression-free survival for all patients was 13.2 months. Overall therapy was well tolerated. Prolonged myelosuppression was more common in patients who received prior nucleoside analogues. Bendamustine is active and produces durable responses in previously treated WM, both as monotherapy and with CD20-directed monoclonal antibodies.     

Targeting c-KIT,PDGFR in cancer of unknown primary: a screening study for molecular markers of benefit

Aims In view of available targeted therapies, we investigated the presence of c-kit, PDGFR gene mutations and protein expression in cancer of unknown primary (CUP) in order to study their contribution in pathogenesis, their prognostic value and potential as therapeutic targets. Methods Mutations in hot spots c-kit exon 11 and PDGFR exons 12 and 18 were studied in paraffin-embedded tumour samples from 50 patients with CUP by means of PCR-based single-strand conformational polymorphism and protein expression by means of streptavidin-biotin immunoperoxidase assays. Molecular markers were screened for possible correlations with patient outcome. Results No shifted band was detected in any of the polyacrylamide gel electrophoreses, indicating absence of c-kit exon 11 and PDGFR exon 12, 18 mutations. Immunohistochemical analysis in 37 tumours revealed positive membranous CD117 expression in 30 samples (81%) of which five exhibited strong (+3), four moderate (+2) and 21 weak (+1) staining. PDGFRa protein staining was seen in 15 out of 30 (50%) cases, mostly weak (13) and rarely moderate (1) or strong (1). The expression of KIT or PDGFRa protein did not correlate with the clinical outcome of the patients in our cohort. Conclusions In a moderate-sized CUP patient cohort, KIT or PDGFRa protein overexpression is rare, does not have gross prognostic significance for survival and is not associated with presence of activating mutations.     

Digital panoramic radiography: a clinical survey

The application of digital panoramic radiography with photostimulable phosphors to dental diagnosis was evaluated in 500 patients. Comparative intraoral films of selected groups of teeth and electronic magnifications of the same portion of the arches were obtained in 63 cases. Digital images improved the quality of dental examinations compared with film radiographs. The possibility of contrast modulation was helpful to compensate for the different radiographic densities of the arches and to improve the visibility of gingival soft tissues. In addition, digital radiography reduced the radiation dose administered to the patient. The use of digital panoramic radiography is proposed as a substitute for film studies in all hospitals where a central unit for digital radiology is available. Correspondence to: R. Nessi     

Selecting a specific pre- or postoperative adjuvant therapy for individual patients with operable gastric cancer

Although the very high locoregional recurrence rates reported with limited D0/D1 surgery can be reduced with extended D2 gastrectomy for operable gastric cancer, overall relapse and survival rates remain poor and can only be improved with adequate perioperative adjuvant treatment. However, despite intensive research, no regimen has been established as standard. Meta-analyses have demonstrated a marginal survival benefit with adjuvant chemotherapy. Two recent large randomized trials for operable gastric cancer, the MAGIC trial and the INT-0116 trial, provide evidence that some patients may benefit from perioperative chemotherapy and chemoradiation, respectively. However, while both trials suggest an overall survival benefit with adjuvant treatment, they don't provide the harm-benefit ratio for specific subsets of patients wih different extent of surgery (D1 or D2) and tumor stage (early [T1,2]/advanced [T3,4]). This lack of evidence complicates current therapeutic adjuvant decisions. Estimating the risk of local and distant recurrence (high, moderate or low) after D1 or D2 surgery in various tumor stages and the expected harm-benefit ratio, the authors provide useful information for decisions on adjuvant chemotherapy with or withour radiotherapy in individual patients. Research on newer cytotoxic and targeted agents may improve treatment efficacy. Simultaneously, advances with microarray-based gene-expression profiling signatures may improve individualized treatment decisions. However, the validation and translation of these genomic classifiers as biomarkers into a completed 'bench-to-bedside' cycle for tailoring treatment to individuals is a major challenge and limits inflated expectations.     

Factors influencing the quality of life of young patients with diabetes

Background: Diabetes is a significant challenge for pediatric health care professionals because it affects youths’ psychoemotional functioning and, consequently, the quality of life (QOL). The aim of the present study was to evaluate the QOL in young patients with diabetes, as well as the factors affecting it. Methods: The study was conducted from April to September 2008 in 98 young patients, 11–18 years of age, who were under the supervision of Diabetological Center, General Pediatric Hospital (Athens, Greece). The Diabetes Quality of Life for Youths Questionnaire was used to evaluate the QOL of youths with diabetes. Results: The mean QOL score was 97.5. There was a negative correlation between the QOL and age (P = 0.02), the duration of diabetes (P = 0.05), body mass index (BMI; P = 0.04), and comorbidities (P = 0.03). In contrast, there was a positive correlation between QOL and increased metabolic control (P = 0.03), participating in sports activities (P = 0.007), and a greater number of insulin infusions (P = 0.04). Conclusions: The QOL of young diabetics was influenced by demographic, somatometric, and other characteristics of diabetes. Increased metabolic control, participating in sports activities, and a greater number of insulin infusions resulted in better QOL. Increased patient age, duration of diabetes, HbA1c values, BMI, and the coexistence of various health problems, as well as the use of an insulin pump, decreased QOL.     

Thermophysical Properties and Molecular Relaxations in Cured Epoxy Resin + PEO Blends: Observations on Factors Controlling Miscibility

Summary: Thermophysical properties and molecular relaxations in aromatic amine‐cured diglycidyl ether of bisphenol‐A (DGEBA) epoxy oligomer and poly(ethylene oxide) (PEO) mixtures were determined by DSC and dielectric techniques (TSC, DRS). The binary blends were judged to be fully miscible in the amorphous state (w_PEO < 40 wt.‐%), as evidenced by the single composition‐dependent glass transition temperatures T_gs. In the amorphous blends, negative deviations of dielectric/thermal T_g‐estimates from the linear mixing rule or the behavior predicted by the Fox equation reveal weaker intermolecular interactions, compared to strong self‐association of hydroxyls in the cured thermoset. Morphological changes in PEO‐rich blends (w_PEO ≥ 40 wt.‐%) are in accordance with their complicated interface structure, previously reported to consist of amorphous PEO regions, branched epoxy resin chains and an imperfect epoxy resin network located between PEO lamellae. In these blends, PEO crystallites exert steric hindrances in the amorphous regions, causing strong T_g upshifts. Changes in the relaxation dynamics of glyceryl segments (e.g., in the activation energy barrier and relaxation strength) are in accordance with the idea that the close matching between the molecular polarities of PEO, epoxy resin and the cure agent significantly contributes to the observed miscibility.

Plots of transition temperatures as function of blend composition.     

Histone deacetylase inhibitors demonstrate significant preclinical activity as single agents, and in combination with bortezomib in Waldenström's macroglobulinemia

We studied the role of histone deacetylase inhibitors in Waldenstrom's macroglobulinemia (WM). Gene expression profiling of bone marrow CD19+ cells from 30 patients and 10 healthy donors showed overexpression of HDAC4, HDAC9, and Sirt5, with validation of HDAC9 overexpression by q-PCR in primary and BCWM.1 cells. Suberoylanilide hydroxamic acid, trichostatin A, panobinostat, and sirtinol demonstrated dose-dependent killing of BCWM.1 cells. TSA showed the greatest potency with IC50 of 70 nM. Importantly, HDAC9 activity was decreased following TSA treatment suggesting an essential role for this HDAC in WM therapy. The combination of bortezomib plus HDAC inhibitors resulted in at least additive tumor cell killing in BCWM.1 cells. TSA and bortezomib-induced apoptosis depended on a similar set of caspase activation, whereas their effect on cell cycle regulators was distinctly different. These results provided a framework for examining HDAC inhibitors as monotherapy, as well as combination therapy with bortezomib in WM.     

Systemic Dissemination in Cancer of Unknown Primary is Independent of Mutational Inactivation of the KiSS-1 Metastasis-suppressor Gene

Cancer of unknown primary represents a heterogeneous group of malignancies characterised by early systemic dissemination and lack of primary site. KiSS1 is a member of the metastasis-suppressor gene family whose functional role is being investigated in human malignancies. We extracted DNA from 50 paraffin-embedded unknown primary tumors and screened KiSS1 exons III and IV for presence of mutations by means of Single Strand Conformational Polymorphism and direct sequencing. Only one tumor specimen harboured a cytosine to guanine point substitution in base 242 of exon IVa, resulting in a proline to arginine switch at codon 81 of the KiSS1 protein (P81R). The remaining 49 tumors harbored wild-type KiSS1 alleles, indistinguishable from those of peripheral blood lymphocytes of 50 healthy controls. Consequently, the propensity for systemic spread of unknown primary tumors may by due to mutations in genes other than KiSS1 or aberrant epigenetic regulation.     

IgA and IgG hypogammaglobulinemia in Waldenstr?m’s macroglobulinemia

Background

Hypogammaglobulinemia is common in Waldenström’s macroglobulinemia. The etiology of this finding remains unclear, but it has been speculated to be based on tumor-induced suppression of the ‘uninvolved’ immunoglobulin production

Design and Methods

We evaluated the incidence of IgA and IgG hypogammaglobulinemia in 207 untreated patients with Waldenström’s macroglobulinemia and investigated the associated clinicopathological findings and impact of therapy. We also sequenced eight genes (AICDA, BTK, CD40, CD154, NEMO, TACI, SH2D1A, UNG) implicated in immunoglobulin deficiency in 19 Waldenström’s macroglobulinemia patients with IgA and/or IgG hypogammaglobulinemia.

Results

At baseline 63.3%, 58.0% and 49.3% of the 207 patients had abnormally low serum levels of IgA, IgG, or both. No association between IgA and IgG hypogammaglobulinemia and disease burden, serum IgM levels, β₂-microglobulin, International Prognostic Scoring System score, or incidence of recurrent infections was observed, although the presence of adenopathy and/or splenomegaly was associated with a lower incidence of hypogammaglobulinemia. Lower IgA and IgG levels were associated with disease progression in patients managed with a ‘watch and wait’ strategy. IgA and/or IgG levels remained abnormally low despite response to treatment, including complete remissions. A missense mutation in the highly conserved catalytic site of UNG was observed in a patient with hypogammaglobulinemia, warranting further study of this pathway in Waldenström’s macroglobulinemia.

Conclusions

IgA and IgG hypogammaglobulinemia is common in Waldenström’s macroglobulinemia and persists despite therapeutic intervention and response. IgA and IgG hypogammaglobulinemia does not predict the risk of recurrent infections in patients with Waldenström’s macroglobulinemia, although lower levels of serum IgA and IgG are associated with disease progression in Waldenström’s macroglobulinemia patients being managed with a ‘watch and wait’ strategy.