Use of octogenarian donors for liver transplantation: a survival analysis.

Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long-term results, especially for hepatitis C virus (HCV)-positive recipients. This was a retrospective, single-center review of primary, ABO-compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60-69 years; 70-79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60-69 years; 233 (27.7%) with donors 70-79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60-69 years; 87.6% and 75.1% for grafts 70-79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5-year graft survival was lower for HCV-positive versus HCV-negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.

Clinical and technical characteristics of intraoperative radiotherapy. Analysis of the ISIORT-Europe database.

BACKGROUND: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. MATERIALS AND METHODS: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. RESULTS: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. CONCLUSION: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

Overdose with levetiracetam: a case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Levetiracetam is an anticonvulsant agent that was first approved for use in the United States in 1999 and has a maximum recommended adult dose of 3000 mg daily. It has been noted to have a relatively mild adverse effect profile, with the most common side effects being somnolence, asthenia, infection, and dizziness. Although it has been widely prescribed, there have been few reports on the safety of this agent in overdose. CASE SUMMARY: We present the case of a 49-year-old man who ingested over 22 500 mg of levetiracetam in a suicide attempt. The patient arrived at the Emergency Department 6·5 h after the ingestion and was noted to have no significant sequelae from the ingestion. Based on the patient's weight, he ingested 358 mg/kg of levetiracetam. WHAT IS NEW AND CONCLUSION: The few cases of levetiracetam overdose reported in the literature were associated with relatively mild, if any, symptoms. However, one patient who overdosed on levetiracetam became obtunded and developed significant respiratory distress that required intubation and ventilatory support. Therefore, clinical vigilance is still required in the cases of levetiracetam overdose.

A novel multisensory device for the assessment and rehabilitation of perceptual and attentional competencies.

The present study aims to assess a novel technological device suitable for investigating perceptual and attentional competencies in people with or without sensory impairment. The TechPAD is a cabled system including embedded sensors and actuators to enable visual, auditory, and tactile interactions and a capacitive surface receiving inputs from the user. The system is conceived to create multisensory environments, using multiple units controlled separately and simultaneously. We assessed the device by adapting a spatial attention task comparing performances in different cognitive load conditions (high or low) and stimulation (unimodal, bimodal, or trimodal). 28 sighted adults were asked to monitor both the central and peripheral parts of the device and to tap a target stimulus (either visual, auditory, haptic, or multimodal) as fast as they could. Our results suggest that this new device can provide congruent and incongruent multimodal stimuli and quantitatively measure parameters such as reaction time and accuracy, allowing to investigate perceptual mechanisms in multisensory environments.Clinical Relevance-The TechPad is a reliable tool for the assessment of spatial attention during interactive tasks. its application in clinical trials will pave the way to its role in multisensory rehabilitation.

The effects of weight loss due to gastric banding and lifestyle modification on red blood cell aggregation and deformability in severe obese subjects.

OBJECTIVE: To investigate the changes in the aggregation index (AI) and the elongation index (EI), in severe obese subjects (MbObS) undergoing laparoscopic adjustable gastric banding (LAGB). AI and EI are measured by Laser assisted Optical Rotational Red Cell Analyzer (LORCA) and are markers of erythrocyte aggregation and deformability, respectively. DESIGN AND SUBJECTS: Before, 3 and 6 months after LAGB plus lifestyle changes (Mediterranean diet plus daily moderate exercise), we evaluated AI, EI, body mass index (BMI), total (ToT) cholesterol (Chol), high-density lipoprotein (HDL)-Chol, low-density lipoprotein (LDL)-Chol, triglycerides and fasting glucose and insulin levels in 20 MbObS. The Student's t-test was used for comparisons between independent groups and the analysis of variance to assess differences in AI and EI at the 3 time points. Pearson's correlation coefficient was used to assess correlation among continuous variables and multiple linear regression analysis to assess predictive factors for AI and EI changes. RESULTS: BMI and all blood parameters showed a statistically significant decline 3 and 6 months after LAGB as compared with basal, except for EI and HDL-Chol that significantly increased. Stepwise selection of predictors shows that at 3 and 6 months, EI values depended on HDL-Chol values at the same time point. In the EI model, blood glucose was also statistically significant at 6 months. CONCLUSION: Our data show a significant improvement in EI after LAGB-induced weight loss, which correlates with an improved lipid pattern and support the idea that the rapid weight loss induced by LAGB plus lifestyle changes might reduce the thromboembolic risk and the high mortality risk found in MbObS.

Recurrent varicose veins of the legs. Analysis of a social problem.

The present study was aimed at assessing the experience of a single referral center with recurrent varicose veins of the legs (RVL) over the period 1993-2008. Among a total of 846 procedures for Leg Varices (LV), 74 procedures were for RVL (8.7%). The causes of recurrence were classified as classic: insufficient crossectomy (13); incompetent perforating veins (13); reticular phlebectasia (22); small saphenous vein insufficiency (9); accessory saphenous veins (4); and particular: post-hemodynamic treatment (5); incomplete stripping (1); Sapheno-Femoral Junction (SFJ) vascularization (5); post-thermal ablation (2). For the "classic" RVL the treatment consisted essentially of completing the previous treatment, both if the problem was linked to an insufficient earlier treatment and if it was due to a later onset. The most common cause in our series was reticular phlebectasia; when the simple sclerosing injections are not sufficient, this was treated by phlebectomy according to Mueller. The "particular" cases classified as 1, 2 and 4 were also treated by completing the traditional stripping procedure (+ crossectomy if this had not been done previously), considered to be the gold standard. In the presence of a SFJ neo-vascularization, with or without cavernoma, approximately 5 cm of femoral vein were explored, the afferent vessels ligated and, if cavernoma was present, it was removed. Although inguinal neo-angiogenesis is a possible mechanism, some doubt can be raised as to its importance as a primary factor in causing recurrent varicose veins, rather than their being due to a preexisting vein left in situ because it was ignored, regarded as insignificant, or poorly evident. In conclusion, we stress that LV is a progressive disease, so the treatment is unlikely to be confined to a single procedure. It is important to plan adequate monitoring during follow-up, and to be ready to reoperate when new problems present that, if left, could lead the patient to doubt the validity and efficacy of the original treatment.

Absence of FGFR3-TACC3 rearrangement in hematological malignancies with numerical chromosomal alteration.

FGFR-TACC, found in different tumor types, is characterized by the fusion of a member of fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to a member of the transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks of FGFR-TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3-TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended.

Ultrasound transmission gel as a bolus device for skin irradiation of irregular surfaces: technical note.

PURPOSE: This paper describes an uncommon radiation treatment of the external ear, with ultrasound (US) transmission gel used as bolus device to compensate for the irregularity of the target surface. MATERIALS AND METHODS: Postoperative radiotherapy for cutaneous carcinoma was performed with a single high-energy electron beam directed over the ear auricle. Due to the irregular surface of the target, a "missing tissue" compensator was employed. Daily, after patient positioning, the concha was filled and flattened with US gel, and a dose of 54 Gy in 27 fractions was delivered. RESULTS: Water equivalence of the gel was verified by comparing the gel's computed tomography (CT) number [Hounsfield units (HU)] and density with the corresponding values for water and another commercial bolus device. Whereas ultrasound gel and water had comparable values (HU: 0; density 1 g/cm(3) for both), the corresponding values for the commercial device were slightly higher (HU: 80; density 1.02 g/cm(3)). CONCLUSIONS: Ultrasound gel proved to be an easy, fast and cheap compensating tool. Its water equivalence allows it to be used as an alternative to water, though easier to position and with lower risk of displacement. Thus, it is recommendable as a practical tool for most irregular sites. Further investigations are warranted to validate this solution in more complex irradiation techniques.

Acute Promyelocytic Leukemia: Update on the Mechanisms of Leukemogenesis, Resistance and on Innovative Treatment Strategies.

This review highlights new findings that have deepened our understanding of the mechanisms of leukemogenesis, therapy and resistance in acute promyelocytic leukemia (APL). Promyelocytic leukemia-retinoic acid receptor α (PML-RARa) sets the cellular landscape of acute promyelocytic leukemia (APL) by repressing the transcription of RARa target genes and disrupting PML-NBs. The RAR receptors control the homeostasis of tissue growth, modeling and regeneration, and PML-NBs are involved in self-renewal of normal and cancer stem cells, DNA damage response, senescence and stress response. The additional somatic mutations in APL mainly involve FLT3, WT1, NRAS, KRAS, ARID1B and ARID1A genes. The treatment outcomes in patients with newly diagnosed APL improved dramatically since the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). ATRA activates the transcription of blocked genes and degrades PML-RARα, while ATO degrades PML-RARa by promoting apoptosis and has a pro-oxidant effect. The resistance to ATRA and ATO may derive from the mutations in the RARa ligand binding domain (LBD) and in the PML-B2 domain of PML-RARa, but such mutations cannot explain the majority of resistances experienced in the clinic, globally accounting for 5-10% of cases. Several studies are ongoing to unravel clonal evolution and resistance, suggesting the therapeutic potential of new retinoid molecules and combinatorial treatments of ATRA or ATO with different drugs acting through alternative mechanisms of action, which may lead to synergistic effects on growth control or the induction of apoptosis in APL cells.

Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20-40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16-2.77; P=0.008), haemoglobin 50 ng ml(-1) (HR, 1.86; 95% CI, 1.21-2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16-2.53; P=0.006), and time-to-progression under first-line chemotherapy

Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer.

Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, associated with unfavorable clinical characteristics in breast cancer. The aim of this study was to evaluate different angiogenic markers in endocrine-positive breast cancer patients. The authors analyzed serum and tumor samples from 71 patients with endocrine-positive operable primary breast cancer to determine the expression and the possible relationship between circulating serum VEGF levels, tumor VEGF expression, microvessel density (MVD), and other immunohistochemical parameters. Basal VEGF serum levels were significantly higher in breast cancer patients than in healthy controls. A significant correlation was observed between basal VEGF serum concentrations, microvessel density (p = 0.01) and p53 status (p = 0.004). Intratumoral VEGF expression was significantly associated with neoplastic embolization (p = 0.041) and circulating VEGF levels (p = 0.047). The results confirm that in primary endocrine-positive breast cancer serum VEGF levels are elevated and show a positive relationship with tumor VEGF and p53 overexpression.

False positive tardus-parvus waveforms after liver transplantation: a case of wide discrepancy between donor and recipient hepatic arteries mimicking anastomotic stenosis.

BACKGROUND: Parvus-tardus waveforms of the hepatic artery after liver transplantation usually indicate an arterial complication and severe impairment of hepatic arterial perfusion with a sensitivity of 91% and a specificity of 99.1%. Thus, it has been emphasized that detection of such waveforms should prompt emergency angiography. MATERIALS AND METHODS: Arterial reconstruction during a liver transplantation was successfully accomplished by an end-to-end anastomosis, performing a "flute-spout" widening of the anastomosis with a 7/0 prolene running suture between a small recipient proper hepatic artery and the donor common hepatic artery. RESULTS: On day 7 posttransplantation color Doppler ultrasonography revealed a parvus-tardus waveform pattern in the hepatic arterial flow. Computed tomographic (CT) angiography showed only a caliber discrepancy between the donor and recipient stumps, excluding an arterial stenosis or thrombosis. Since normal liver function persisted, the patient underwent routine follow-up. After 15 months the patient was alive and well; hepatic artery spectral waveforms were unchanged and liver functions were consistent with a mild hepatitis C virus (HCV) recurrence. CONCLUSIONS: This is a report of false positive tardus-parvus waveforms, due to a discrepancy between the donor and recipient arteries despite a wide anastomosis. Knowledge of technical reconstruction details may be helpful for correct interpretation of color Doppler findings. CT angiography should be considered before more invasive examinations.

Transcranial doppler sonography is useful for the decision-making at the point of care in patients with acute hepatic failure: a single centre's experience.

Acute hepatic failure (ALF) is an uncommon disease characterized by a rapid deterioration of the hepatic function with severe derangements of the mental status in previously healthy subjects due to massive hepatocytes necrosis. Neurological impairment, due to intracranial hypertension and cerebral ischemia, is a key factor because it is a main criterion to decide when to proceed to liver transplantation, which is only treatment for these patients. Therefore, neurological monitoring holds an essential role in the clinical management of ALF patients but it needs to be performed at the point-of-care in the majority of the cases as such critically ill patients cannot be moved away from the ICU because they frequently need continuous hemodynamic, ventilatory and renal support. We herein report and discuss our experience relating to the use of transcranial sonography as a neuro-monitoring tool in ALF patients. In our series this technique allowed a repeatable and reliable non-invasive assessment of cerebral blood flow changes at the bedside thus avoiding the complications associated with the use of an intracranial probe to measure intra-cranial pressure and making it possible to correctly evaluate the timing and feasibility of liver transplantation.

[Consideration on the treatment of chronic occlusive lesions of the iliac arteries]. / Considerazioni sul trattamento delle lesioni arteriose ostruttive croniche dell'asse iliaco.

This study addresses the problem of the best treatment for chronic unilateral obstructive lesions of the aorto-iliac arterial axis. After making a review of the literature, some considerations are made. In recent years this disease has increasingly been treated by endovascular methods with dilation (angioplasty) and stents. However, the classic indications (short stenotic obstruction), supported by national and international guidelines, are being continually widened by operators acquiring growing skills with this method. Nevertheless, no long term studies have demonstrated a clear superiority, in severe cases, of endovascular methods over traditional surgical methods (by-pass), as regards either long term results or costs. Among the traditional methods, many surgeons prefer the femoro-femoral by-pass to the orthopic aorto-femoral by-pass, particularly because of its lesser invasiveness. However, it should be noted that comparisons of the two methods have yielded results in favour of the orthotopic procedure, above all about long term results.

Cost analysis of tumor downsizing for hepatocellular carcinoma liver transplant candidates.

We report the results of a prospective, intent-to-treat (ITT) trial on the costs of selective tumor downsizing (DS) before liver transplantation (LT) for patients affected with hepatocellular carcinoma (HCC). The trial started in January 1997 including adult patients with nodular-type HCC within and beyond the Milan criteria. Patients were downsized with transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and/or radiofrequency ablation (RFA) according to clinical predictors. TACE and RFA were performed as inpatient procedures, while PEI was performed on an outpatient basis. Costs of DS were obtained according to the Tuscany Health Reimbursement Fee Catalog adjusted to yearly inflation rates from 1997 through 2005. Data analysis was performed at 1 year after the last enrollment of 198 patients, including 161 (81.3%) who were transplanted: 34 (17.2%) dropped out and 3 (1.5%) were still on the waiting list. One hundred and fifty-two patients (76.7%) underwent DS for a total of 201 procedures: 159 TACE, 39 PEI, and 3 RFA. Overall costs in Euros (euro) of waitlisting were 861,801.24 euro: 548,460 euro (63.7%) for pretransplantation evaluation; 197,994.84 euro (22.9%) for control visits and hospitalizations; and 115.346.4 euro (13.4%) for DS. Mean costs of DS were 758.58 euro +/- 270 euro per downstaged patient (747.53 euro +/- 257.1 euro Milan; 774.01 euro +/- 287.71 euro non-Milan); 582.85 euro +/- 398.87 euro per waitlisted patient (520.28 euro +/- 406.23 euro Milan; 520.28 +/- 364.48 euro non-Milan); and 716.4 euro per transplanted patient (580.67 euro Milan; 1026.76 euro non-Milan; +76.8%). A selective policy of tumor DS increased the costs of LT waitlisting by 13.4%, but due to higher dropout rates among non-Milan patients, the cost utility of DS was 76.8% higher in the Milan group.

Expression cDNA cloning of a novel oncogene with sequence similarity to regulators of small GTP-binding proteins.

We generated a cDNA expression library from a human mammary epithelial cell line for detection of novel oncogenes by focus formation assay in NIH3T3 cells. A morphologically unique focus was identified and the transforming plasmid was isolated. The transforming gene, designated TIM, encoded a predicted protein species of 60 kDa containing a Dbl-Homology (DH) motif. This motif is also present in other growth regulatory molecules including Bcr, Cdc24, Vav, Ras-grf, and Ect2 which have been implicated as regulators of small GTP-binding proteins. NIH3T3 cells transfected with TIM expression plasmid showed altered growth properties in vitro and were tumorigenic when injected into nude mice. The 6.5 kilobasepair (kb) transcript of the TIM gene was mainly expressed in kidney, liver, pancreas, lung, and placenta. By analysing a panel of human-hamster somatic cell hybrids, we localized the TIM gene to human chromosome 7.

Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial.

PURPOSE: We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP)-induced neurotoxicity. PATIENTS AND METHODS: Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m2 in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m2) and 15 (CDDP dose, 600 mg/m2) weeks of treatment. RESULTS: At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH. CONCLUSION: This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs.

Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial.

PURPOSE: Diarrhea is a prominent feature of fluorouracil (5FU) gastrointestinal toxicity, especially when 5FU is combined with leucovorin (LV) or interferon (IFN). No treatment for this condition has been well defined, although drugs, such as diphenoxylate or loperamide, generally are used. The efficacy of octreotide in the treatment of 5FU-induced diarrhea recently has been reported. We performed a randomized trial that compared octreotide with loperamide, the drug most commonly used for therapy for this disorder. PATIENTS AND METHODS: Forty-one patients with grade 2 (four to six stools per day) or grade 3 (seven to nine stools per day; National Cancer Institute toxicity criteria) diarrhea after chemotherapy with a 5FU-containing regimen for colorectal cancer in 28 cases, gastric cancer in six cases, pancreatic cancer in five cases, and breast cancer in two cases, were entered onto the study. Twenty-one patients received octreotide at a dosage of 0.1 mg subcutaneously twice per day for 3 days, and 20 patients received loperamide 4 mg orally initially and then 2 mg every 6 hours for 3 days. The two arms were comparable for age, sex, and primary tumor. Patients were evaluated for response each treatment day; all patients were assessable. RESULTS: Diarrhea resolved in 19 patients in the octreotide arm (one within the first day; four within the second day; and 14 within the third day) versus only three (all after the third day of therapy) in the loperamide arm (P < .005). Median frequency of stools in the 3 days of therapy was four, three, and zero in the octreotide arm and five, five, and five in the loperamide arm. No side effects were observed in both arms. Ten patients on the loperamide arm and only one on the octreotide arm required hospitalization for parenteral replenishment of fluids and electrolytes. CONCLUSION: Octreotide seems to be more effective than loperamide in control of diarrhea and elimination of the need for replenishment of fluids and electrolytes.