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Purpose: The aim of this study was to assess the fractal dimension (Df) of disks with 3 different surface topographies., Materials and Methods: Thirty disk-shaped samples (10 × 2 mm) with 3 different surface topographies (Dental Tech, Misinto, Italy) were analyzed by scanning electron microscopy: group A, machined surface; group B, titanium plasma-spray surface; group C, acid-etched and sandblasted surface (Blasted Wrinkled Surface)., Results: The amplitude roughness parameter (Sa) of the machined surfaces was 0.6 μm, while the developed surface area ratio (Sdr) was 14%; for the titanium plasma-spray surfaces, the values were, respectively, 5.3 μm and 97%, and for the Blasted Wrinkled Surfaces, 1.5 μm and 63%. Images at 1.000, 20.000, and 50.000 magnifications were processed for quantitative analysis of Df using the box-counting method. At 1.000×, Df for group A, B, and C was 1.86, 1.80, and 1.81, respectively; at 20.000×, Df for group A, B, and C was 1.85, 1.71, 1.58, respectively; and at 50.000×, Df was 1.83, 1.61, and 1.51 for A, B, and C groups. Statistically significant differences were found for Df values., Conclusions: Df provides not only an index of roughness size values but also a measure of roughness spatial organization; therefore, it could be a promising method to differentiate between rough surfaces capable of supporting osseointegration.

Background: Since gemcitabine became the standard treatment for metastatic pancreatic adenocarcinoma, combination chemotherapy obtained conflicting impact on survival (OS)., Aims: To evaluate Italian treatment trends in metastatic pancreatic cancer., Methods: Data on treatment outcome of 943 chemo-naive patients with pathological diagnosis of stage IV pancreatic adenocarcinoma treated between 1997 and 2007 in Italian centres were analysed., Results: Four treatment groups could be identified: (1) single agent gemcitabine (N=529); (2) gemcitabine-platinating agent doublets (N=105); (3) gemcitabine-free three-drug intraarterial combination (N=75); (4) four-drug gemcitabine-cisplatin-fluoropyrimidine based combinations (N=170). Median and actuarial 1 y OS of the whole population were 6.2 months and 20%, respectively. Gemcitabine (median OS 5.1 months) appeared significantly inferior to gemcitabine-free triplets (median OS 6.0 months; p=.04), gemcitabine-platinating agent doublets (median OS 7.4 months; p=.00001), or gemcitabine-based four drug combinations (median OS 9.1 months; p<.00001)., Conclusion: These data mirror the Italian clinical practice in the therapeutic management of pancreatic cancer and suggest that four-drug combination chemotherapy may be included amongst the candidate regimens for phase III testing., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2; also known as ERBB2), was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer., Methods: ToGA (Trastuzumab for Gastric Cancer) was an open-label, international, phase 3, randomised controlled trial undertaken in 122 centres in 24 countries. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation. Participants were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab. Allocation was by block randomisation stratified by Eastern Cooperative Oncology Group performance status, chemotherapy regimen, extent of disease, primary cancer site, and measurability of disease, implemented with a central interactive voice recognition system. The primary endpoint was overall survival in all randomised patients who received study medication at least once. This trial is registered with ClinicalTrials.gov, number NCT01041404., Findings: 594 patients were randomly assigned to study treatment (trastuzumab plus chemotherapy, n=298; chemotherapy alone, n=296), of whom 584 were included in the primary analysis (n=294; n=290). Median follow-up was 18.6 months (IQR 11-25) in the trastuzumab plus chemotherapy group and 17.1 months (9-25) in the chemotherapy alone group. Median overall survival was 13.8 months (95% CI 12-16) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0.74; 95% CI 0.60-0.91; p=0.0046). The most common adverse events in both groups were nausea (trastuzumab plus chemotherapy, 197 [67%] vs chemotherapy alone, 184 [63%]), vomiting (147 [50%] vs 134 [46%]), and neutropenia (157 [53%] vs 165 [57%]). Rates of overall grade 3 or 4 adverse events (201 [68%] vs 198 [68%]) and cardiac adverse events (17 [6%] vs 18 [6%]) did not differ between groups., Interpretation: Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer., Funding: F Hoffmann-La Roche., (Copyright 2010 Elsevier Ltd. All rights reserved.)

A series of 650 patients treated between 1997 and 2007 at 10 Italian centers was analyzed to assess treatment trends and efficacy in stage III pancreatic adenocarcinoma. Data on patient characteristics, treatment and outcomes were collected. The inclusion criteria were pathological diagnosis of stage III pancreatic adenocarcinoma; age more than 18 years, Eastern Cooperative Oncology Group performance status less than 3, and no past therapy. Most patients (95%) received up-front chemotherapy, which mainly consisted of gemcitabine alone (N=323), gemcitabine-based four-drug combinations (N=107), gemcitabine-platinum compound doublets (N=87), or intra-arterial gemcitabine-free triplets (N=57). The use of gemcitabine-platinum compound doublets increased over time (1997-2001: 2%; 2002-2007: 21%) whereas an inverse trend was observed for gemcitabine (71-61%). No overall survival (OS) difference was observed between patients enrolled in clinical trials and those not enrolled. The median and 1-year OS were 9.5 months and 35.5% for patients treated with gemcitabine; 8.9 months and 36.8% for those treated with gemcitabine-free intra-arterial triplets; 13.3 months and 55.8% for those treated with gemcitabine-platinating agent doublets; and 16.2 months and 62.6% for those treated with gemcitabine-based four-drug combinations. Moreover, the median and 1-year OS were 12.7 months and 51.4% in patients who underwent planned consolidation chemoradiation, and 8.4 months and 30.4% in patients who did not. The use of a strategy consisting of a gemcitabine-platinating agent containing chemotherapy followed by consolidation chemoradiation has been increasing over time and may represent a suitable choice in the therapeutic management of stage III pancreatic adenocarcinoma.

In this study, a biomonitoring project using the moss Scorpiurum circinatum was carried out to evaluate the deposition and biological effects of heavy metals in the area of Acerra (Naples, S Italy), one of the vertices of the sadly called "Italian triangle of death" owing to the dramatic increase in tumours. The results clearly indicated that the study area is heavily polluted by heavy metals, a large proportion of which is likely present in the atmosphere in particulate form. The ultrastructural organization of exposed samples was essentially preserved, but cell membrane pits, cytoplasm vesicles and concentric multilamellar/multivesicular bodies, probably induced by pollution, were found, which may be involved in the tolerance mechanisms to metal pollution in this moss species. Although severe biological effects were not found at the ultrastructural level in the exposed moss, effects on humans, especially after long-term exposure, are to be expected.

Capecitabine (N -pentyloxycarbonyl-5-deoxy-5-fluorocytidine), an oral prodrug of 5-fluorouracil, has provided compelling efficacy data for the treatment of metastatic breast cancer and stage III or IV colorectal cancer, both as monotherapy and in combination regimens. The preferential conversion of capecitabine to 5-fluorouracil in neoplastic tissues renders this fluoropyrimidine particularly appealing for clinical use. The enzyme thymidine phosphorylase, which mediates the final step of the capecitabine activation pathway, is expressed in higher concentration in neoplastic than in healthy tissues. This makes capecitabine more tumor specific than other chemotherapeutic agents. Accordingly, capecitabine is generally well tolerated. In particular, the incidence of myelosuppression and alopecia is low, and the most common side effects, hand-foot syndrome and diarrhea, are usually manageable. Given its good toxicity profile, capecitabine was assessed in combination with several chemotherapeutic or biologic agents. In addition, the observation that thymidine phosphorylase is upregulated after treatment with other anticancer drugs, namely taxanes, provided a rationale for the prominent antitumor activity recently observed for the combination of capecitabine with these agents. This review provides an evidence-based update of clinical trials investigating the role of capecitabine in the treatment of breast and colorectal cancer, with special emphasis on pharmacological and safety issues that form the basis of currently used schedules.

Purpose of Review: To summarize the available evidence on cooccurring gastrointestinal toxicities and their potential link with other symptoms in cancer patients. The information obtained from colorectal cancer patient cohorts will be used as an example., Recent Findings: In recent years, it has become clear that gastrointestinal toxicities do not occur in isolation in cancer patients. Rather, they may link or associate with many other disturbances. Data have emerged that suggest that many of the complications of cancer chemotherapy occur in clusters and seem to support the sharing of common pathogenesis for clustering toxicities., Summary: During the last few years, research in symptom clusters and cooccurring linked toxicities has markedly changed, progressively shifting from a simplistic descriptive picture to more comprehensive and pathogenetically driven analyses. Still, many questions remain to be answered, and whether and how toxicity aggregations vary during the treatment course remains to be elucidated.

Background: New systemic treatments for advanced colorectal cancer have conferred a survival advantage, allowing patients to reach a median survival of almost 2 years. Due to this remarkable life extension, the incidence of brain metastases, though still low, is progressively increasing over time. There is little reported data on the optimal strategy to manage brain lesions from colorectal cancer., Methods: To explore the role of an aggressive approach to colorectal cancer brain metastases, we retrospectively collected and analyzed data from 30 patients who underwent neurosurgical resection + whole-brain radiotherapy between March 1998 and December 2006. Univariate (logrank) and multivariate (Cox's model) analyses were used to identify prognostic factors., Results: Median age at the time of surgery was 66 years, median ECOG PS was 1, most patients (87%) had concomitant lung and/or liver metastases. Median number of previous chemotherapies was two, with half of the patients being exposed both to oxaliplatin and irinotecan. A median of 27 Gy of radiotherapy were administered to 16 patients after resection. At the time of the analysis, 29 out of 30 patients had died, with a median survival time after brain metastasectomy of 167 days (8-682). Only one patient died within a month from surgery. Median survival was significantly longer in patients who received postsurgical radiotherapy (7.6 vs. 4.7 months, P = 0.014)., Conclusions: Neurosurgical management of symptomatic brain metastases from colorectal cancer is feasible, relatively safe, and offers a chance of prolonged survival. Patients who received radiotherapy after resection experienced a better outcome.

Collection of collateral effects related to toxicities suffered by patients being exposed to anticancer treatments is of crucial importance in clinical practice but also in oncological research. The present paper describes a web application called PaTOS for self-report of anticancer therapy toxicities, and its evaluation in a preliminary interface analysis and then in a feasibility study.

Trace element accumulation in the lichen Pseudevernia furfuracea (L.) Zopf was studied in the district of Acerra (province of Naples, southern Italy), one of the points forming Italy's Triangle of Death. P. furfuracea thalli, collected from Mt. Faito (province of Naples), were transplanted and exposed in bags at different sites in Acerra district, classified into three different site types (urban, rural and industrial). We aimed to test the hypothesis that P. furfuracea, when transplanted in the district of Acerra, would respond to air pollution accumulating trace elements and that element concentrations in the exposed lichens were different in relation to the three different environments, characterised by different pollution sources. Samples were exposed for six months, periodically collected and examined by ICP MS spectrometer assays to measure concentrations of 10 trace elements (Al, As, Cd, Cr, Cu, Fe, Mn, Pb, V and Zn). The exposed samples showed increases in concentrations of all the examined elements; the trace element concentrations were evaluated by calculating exposed to control (EC) ratios, for each site and each trace element, to better understand the accumulation rates. EC ratios were evaluated after 3 and 6 month exposures, at the end of spring and summer respectively: 6 month EC values were the highest. The urban sites showed EC ratios generally higher than industrial and rural; the most accumulated elements were Pb and Cu (at the urban sites), Cu and Zn (at the industrial sites), and Cu and As (at the rural sites). The chemical data were then processed using a multivariate approach (ordination, PCA) to better understand environmental gradients. Bioaccumulation data and PCA analysis showed the sampling sites separated by different trace element abundance. Trace element abundance patterns in the three site types are discussed in relation to the land use and the pollution sources.

Aim: To investigate the prevalence of celiac disease (CD) in adult patients referred to an open access gastroenterology clinic in the south of Italy and submitted to esophago-gastro-duodenoscopy (EGD) for evaluation of refractory functional dyspepsia., Methods: Seven hundred and twenty six consecutive dyspeptic patients (282 male, 444 female; mean age 39.6 years, range 18-75 years) with unexplained prolonged dyspepsia were prospectively enrolled. Duodenal biopsies were taken and processed by standard staining. Histological evaluation was carried out according to the Marsh-Oberhuber criteria., Results: The endoscopic findings were: normal in 61.2%, peptic lesions in 20.5%, malignancies in 0.5%, miscellaneous in 16.7%. CD was endoscopically diagnosed in 8 patients (1.1%), histologically in 15 patients (2%). The endoscopic features alone showed a sensitivity of 34.8% and specificity of 100%, with a positive predictive value (PPV) of 100% and a negative predictive value (NPP) of 97.9%., Conclusion: This prospective study showed that CD has a high prevalence (1:48) in adult dyspeptic patients and suggests the routine use of duodenal biopsy in this type of patient undergoing EGD.

Around 4,800 abstracts on preclinical and clinical research in different oncology areas were presented and discussed by oncology clinicians and scientists at the 44th American Society of Clinical Oncology meeting, the largest international forum in the field. As expected, the meeting provided valuable insights into future developments as well as enlightening clinicians regarding current controversies. This manuscript is an opinion-based review of the studies presented at the meeting, focusing on findings from randomized phase III trials and translational researches that, in the authors' opinion, are most likely to modify clinical practice or help scientists in designing future translational and clinical studies.

Goals of Work: The way to inform cancer patients varies widely among different countries. In most Mediterranean countries, the traditional approach has been of partial disclosure of the truth. The intent of our work was to find if the attitude in Italy has changed in recent years and if differences still exist among different geographical regions in our country. Both patients' and physicians' attitudes vary in Italy depending on geographical area. In the South, the focus is on traditional values and full involvement of patients' family, with limited communication to (and limited autonomy of) the patient. Such attitude is less pronounced in Central Italy, whereas the North is more oriented to open communication and full decisional autonomy of the patient., Materials and Methods: Approximately 600 consecutive patients in three different centres in Northern, Central and Southern Italy (respectively, Udine, Ancona and Catanzaro) were asked to answer a 26-item questionnaire on communication aspects to investigate the quality of the information given and potential differences between geographical areas., Results: Questionnaires were completed by 587 patients (median age 60 years, 57% women), mainly with gastrointestinal (32%) or breast cancer (30%). About 370 patients (63%) had active disease at time of interview. A high proportion of patients were correctly informed on diagnosis (86%) and therapy (84%). On the contrary, patients fully aware of their prognosis were only about 43%. Nevertheless, most patients (60%) stated they were completely satisfied with the information received. There were differences between geographical areas on various information aspects, with patients from Southern Italy being, in general, less informed., Conclusions: In Italy, the cultural attitude towards communication in oncology is changing on both the physician and the patient side. There are still significant geographical differences, but there is a general trend suggesting improved awareness about diagnosis and treatment, with the notable exception of prognosis.

Background: Cost-containment strategies are required to face the challenge of rising drug expenditures in Oncology. Drug wastage leads to economic loss, but little is known about the size of the problem in this field., Methods: Starting January 2005 we introduced a day-to-day monitoring of drug wastage and an accurate assessment of its costs. An internal protocol for waste minimisation was developed, consisting of four corrective measures: 1. A rational, per pathology distribution of chemotherapy sessions over the week. 2. The use of multi-dose vials. 3. A reasonable rounding of drug dosages. 4. The selection of the most convenient vial size, depending on drug unit pricing., Results: Baseline analysis focused on 29 drugs over one year. Considering their unit price and waste amount, a major impact on expense was found to be attributable to six drugs: cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab. The economic loss due to their waste equaled 4.8% of the annual drug expenditure. After the study protocol was started, the expense due to unused drugs showed a meaningful 45% reduction throughout 2006., Conclusion: Our experience confirms the economic relevance of waste minimisation and may represent a feasible model in addressing this issue.A centralised unit of drug processing, the availability of a computerised physician order entry system and an active involvement of the staff play a key role in allowing waste reduction and a consequent, substantial cost-saving.

Background: Colorectal cancer patients undergoing chemotherapy (CT) are likely to experience multiple concurrent toxicities that, rather than appearing singularly, may be associated with one another. Graphic and tabular representations of distance matrices were used to identify associations between toxicities and to define the strengths of these relations., Methods: Using a standardized data collection tool, electronic medical charts of 300 consecutive patients receiving either the combination of leucovorin, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX); the combination of leucovorin, 5-FU, and irinotecan (FOLFIRI); or 5-FU) were retrospectively reviewed to record baseline demographic and clinical information. Treatment-related toxicities were recorded using National Cancer Institute Common Toxicity Criteria during the first cycle of CT. Using a distance matrix approach, an analysis of CT-induced toxicity associations was elaborated., Results: The graphic analysis, in which associations between toxicities were represented as links, identified 6 major hubs (fever, dehydration, fatigue, anorexia, pain, and weight loss), defined as central nodes with more connections than expected by chance. These were highly linked with minor nodes and provided evidence suggesting the existence of symptom clusters associated with CT-induced toxicities., Conclusions: The application of distance matrix analyses to define CT-induced toxicity associations is new. The technique was effective in defining the global landscape of the binary relations among toxicities associated with Cycle 1 therapy. The coherent clinical picture emerging from the network provides a strong suggestion that the toxicities in each cluster share a common pathobiologic basis, which may provide an opportunity for intervention. These findings could become useful for the early prediction of co-occurring toxicities and, in the future, as a phenotyping framework for the pharmacogenomic analysis of individual responses to chemotherapy.

This study compared the heavy metal bioaccumulation capacity in the epiphytic moss Scorpiurum circinatum and the epiphytic lichen Pseudevernia furfuracea, exposed in bags for 3 months in the urban area of Acerra (S Italy). The content of Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Ti, V, and Zn was measured by ICP-MS. The results showed that both species accumulated all the heavy metals assayed. The moss had the highest bioaccumulation capacity for all metals and showed a more constant and linear accumulation trend than the lichen. Intra-tissue heavy metal bioaccumulation was assessed by X-ray microanalysis applied to ESEM operated in high and low vacuum and ESEM modes.

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years, PS >or=50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) <12 months received a combination of raltitrexed (3 mg m(-2)) and oxaliplatin (130 mg m(-2)) every 3 weeks until progression, toxicity, or a maximum of six cycles. A total of 41 patients received 137 cycles of chemotherapy. Dose intensity for both drugs was 92% of the intended dose. Main grade >2 toxicity was: neutropenia in five patients (12%), thrombocytopenia, liver and vomiting in three (7%), fatigue in two (5%). In total, 10 patients (24%) yielded a partial response, 11 a stable disease. Progression-free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS >6 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed-oxaliplatin regimen may constitute a treatment opportunity in gemcitabine-resistant metastatic pancreatic cancer. Previous PFS interval may allow the identification of patients who are more likely to benefit from salvage treatment.

The health of 22 free-ranging adult rheas (Rhea americana) examined and sampled during a translocation/reintroduction project and six juvenile rheas kept in semicaptivity was investigated, and details of their haematology and plasma biochemistry are presented. Serological testing for antibodies to infectious agents was negative for infectious laryngotracheitis, avian adenovirus, avian influenza, avian reovirus, infectious bursal disease, infectious bronchitis virus, paramyxovirus types 1, 2, and 3, fowlpox and Salmonella Pullorum. Antibodies to Chlamydophila species were found in 25 of 27 of the birds, and 22 of 25 had antibodies to Aspergillus species. Ova of gastrointestinal nematodes of the genus Capillaria were identified, and the anoplocephalid cestode Monoecocestus cf rheiphilus was identified in R americana for the first time.

Background and Objective: Sedation is commonly used to facilitate diagnostic procedures in children. The aim of our study was to investigate sedation in children using propofol alone or combined with fentanyl or midazolam with regard to efficacy, adverse reactions or side-effects related to the drugs, ease of operation for the endoscopist, and time to discharge from the post-anaesthesia care unit., Methods: We prospectively studied 240 children, aged 1-12 yr of age, undergoing endoscopic procedures of the upper gastrointestinal tract. The patients were given an oral premedication with midazolam (0.5 mg kg(-1)) and were then randomly allocated to one of the three study groups: propofol alone (Group P), propofol with fentanyl 1 mug kg-1 (Group PF) or propofol with midazolam 0.1 mg kg(-1) (Group PM). Additional doses of propofol given during the procedure were recorded. Adequacy of sedation and ease of procedure (easy, adequate, impossible) were evaluated by the endoscopist, who was blinded as to the drugs used., Results: The duration of the procedure and the recovery period were similar in the three groups. The number of patients requiring supplemental doses of propofol to permit safe completion of gastroscopy was 31 in Group P (=39%; eight of these required two additional doses), 14 in Group PM (=18%), and 11 in Group PF (=13%) (P < 0.05). There was a lower incidence of adverse events in Group PM and in Group PF than in Group P (P < 0.05)., Conclusions: Propofol in combination with fentanyl or midazolam gives better sedation and ease of endoscopy than propofol alone.

Recurrent malignancy at esophagojejunal anastomosis represents an incurable stage of disease. Treatment options are limited. Surgery presents a high rate of morbidity and mortality and frequently fails to alleviate symptoms. Radiochemotherapy relieves dysphagia slowly and offers disappointing clinical results. The use of Self Expanding Metallic Stent (SEMS) has shown to be effective, safe and offers a good quality of residual life. We herein report three cases of malignant esophagojejunal anastomotic strictures successfully treated with metallic coil stent (Esophacoil).

Galectins are a family of animal beta-galactoside-binding lectins involved in malignant transformation and progression. The present study evaluated the immunohistochemical expression of galectin-3 in a consecutive series of 81 radically resected non-small cell lung carcinomas (NSCLCs). The main pattern of galectin-3 expression was cytoplasmic (median percentage of cells with cytoplasmic positivity: 80.0%). The median percentage of tumor cells with nuclear and cytoplasmic co-expression of galectin-3 was 3.5%. No cases with exclusive nuclear immunostaining were observed. Functional interaction between galectin-3 and the thyroid transcription factor-1 (TTF-1) was previously demonstrated by cotransfection experiments. In the present study, concomitant expression of nuclear galectin-3 and TTF-1 was independently associated with a worse clinical outcome (HR 2.0; P = 0.01).

Aim: To evaluate the relative activity of the sequential administration of doxorubicin and cyclophosphamide (AC) followed by docetaxel alone, as primary systemic therapy in patients with breast cancer, using an in vivo chemosensitivity predictive assay., Patients and Methods: Patients with stage II-III breast cancer received two cycles of AC (60/600 mg/m2 every 3 weeks) followed by two cycles of docetaxel (100 mg/m2 every 3 weeks). All patients underwent comprehensive breast imaging prior to chemotherapy, after two AC and after docetaxel., Results: Forty-two patients were accrued and evaluated by intention-to-treat analysis. After two cycles of AC, the median tumor shrinkage was 18.3%, whereas treatment with docetaxel provided an additional median tumor shrinkage of 34.2%. Pathological complete remission was observed in 5 patients (11.9%), whereas 26 patients (61.9%) experienced a partial response., Conclusion: The relative contribution of docetaxel to tumor mass reduction seemed to be greater than that of AC. However, the slow rate of tumor shrinkage observed may indicate that the activity of the first 2 cycles of AC is carried over into the part of treatment with docetaxel.

Analysis of tumour samples by a proteomic technology, which combines two-dimensional gel electrophoresis and mass spectrometry analysis, is a promising approach for molecular characterization of cancer. Proteomic analysis of neoplasms is usually performed on surgical material. The possibility to perform proteomic analysis on pre-operative samples might be useful for diagnostic purposes or for determination of tumour sensitivity to therapy. In this study, we report how tissues from core biopsy of breast lesions can be routinely used to obtain accurate protein expression profiles by proteomic analysis. Protein profiles from fibroadenomas were compared to those from ductal infiltrating carcinomas. By using mass spectrometry, identification of proteins overexpressed in carcinomas with respect to fibroadenomas was obtained. Thus, our study provides a methodology to perform proteomic analysis on pre-operative samples of breast lesions.

We present results obtained in our first series of 25 patient treated by prolassomucosectomy for haemorrhoidal prolapse with a follow up of 18-36 months. Control of the disease and functional results proved to be optimal. After small early haemorrhages from the suture line, we started adding stitch sutures with haemostatic intent to all three vascular pedicles. Early or late additional complication were not observed.

Background: It is well recognized that distinguishing benign from malignant papillary lesions of the breast may pose challenging diagnostic problems. To prospectively evaluate the potential role of mammography, ultrasound and image-guided core biopsy in the diagnosis of papillary lesions of the breast., Methods: 1,442 women consecutively underwent 14-gauge core biopsy and in 51 cases (3.5%) a diagnosis of papillary lesion was formulated. Both radiologists and pathologists independently expressed their degree of suspicion of malignancy (not suspicious, low, moderate, high) on the basis of radiological and core biopsy findings, respectively. Surgical excision of the lesion was used as gold standard and diagnostic agreement was assessed by the kappa statistic., Results: At surgery, 19 of the 49 (38.7%) resected cases had a diagnosis of malignancy. A poor agreement was found between mammography and core biopsy results in the categorization of suspicion of malignancy (k = 0.03). Similar data were obtained between ultrasound and core biopsy (k = 0.07). A poor agreement was also observed between radiological and surgical results (k < 0.20). In contrast, a good agreement was found between core biopsy and surgical samples (k > 0.70). However, 5 (26%) out of the 19 malignant cases at surgery were judged as benign or probably benign on core biopsy. Depending on how the categories of suspicion on core biopsy were set up, the range of sensitivity was 74-89%, whereas specificity ranged from 91 to 97%., Conclusions: Image-guided large core biopsy allows for a correct diagnosis in the majority of papillary lesions. However, its sensitivity is not good enough for surgical excision to be avoided., (Copyright 2003 S. Karger AG, Basel)

Objective: To evaluate the prognostic value of the balance between apoptosis and proliferation in non-small-cell lung cancer (NSCLC)., Methods: Paraffin-embedded sections from a consecutive series of radically resected NSCLCs were scored for apoptosis (in situ DNA nick end labeling assay) and proliferation (immunohistochemistry for MIB-1). A total of 1,000 cells were counted per case, to obtain apoptotic (AI) and MIB-1 indices. Other potential prognostic indicators (pT, pN, pStage and histology) and p53 status were also evaluated., Results: Univariate analysis showed that adenocarcinomatous histotype (p = 0.03), nodal involvement (p = 0.04), higher pStage (p = 0.001) and the combination of low AI and high MIB-1 expression (p = 0.03) were associated with poorer outcome. The significant prognostic value of the combination 'low AI/high MIB-1' was also confirmed in a multivariate analysis after adjustment for other covariates., Conclusion: These results underline the importance of considering apoptosis and proliferation together to identify a subgroup of NSCLC associated with poor survival., (Copyright 2002 S. Karger AG, Basel)

The purpose of the study was to evaluate the prognostic role of the DNA repair protein APE/Ref-1 in breast carcinomas. Immunohistochemical analysis for APE/Ref-1 was performed in a series of 133 consecutive stage I-III breast carcinomas. The relationship between APE/Ref-1 and other prognostic and predictive factors such as tumor size, nodal status, histologic grade, p53 expression, hormonal receptor status, vascular invasion and necrosis was investigated. The prognostic value of APE/Ref-1 was studied by univariate and multivariate analysis. The predominant pattern of APE/Ref-1 immunohistochemical expression was nuclear, although cytoplasmic and mixed nuclear/cytoplasmic localization was also observed. The percentage of cells with APE/Ref-1 cytoplasmic stain directly correlated with the percentage of p53 positive cases (rho=0.28, p=0.013). The small group of women whose tumors showed mixed nuclear/cytoplasmic APE/Ref-1 localization (n=5) experienced a significantly poorer survival (p=0.014) and Cox proportional hazard model analysis identified APE/Ref-1 as an independent prognostic factor. The results suggest that subcellular localisation of APE/Ref-1 may influence the aggressiveness of breast carcinomas.

Background and Aim: Few reports have shown that EsophaCoil is an effective and safe prosthesis for palliation of malignant oesophageal dysphagia. A single centre experience using this type of prosthesis is reported., Patients and Methods: Between January 1995 and September 2000, 42 consecutive patients, 41 with unresectable oesophageal cancer and one with oesophageal stenosis secondary to lung cancer, were treated with 44 EsophaCoils (2 patients received 2 stents). Tumours were located in lower third of oesophagus and/or gastric cardia in 22 cases, in middle third in 18 and in upper third in 2. Mean stricture length was 5.3 cm. Implantation was performed on hospitalized patients., Results: EsophaCoil placement was successful all 44 times and was followed by complete expansion of the prostheses. There were no major procedure-related complications or deaths. Dysphagia score improved from mean of 2.9 to 1.3 within 24 hours of stent implantation. Median hospital stay was 2.7 days. Late complications occurred in 14 patients (34.2%): 3 migrations into stomach, 7 tissue overgrowth, 2 late perforations and 2 food impactions. Mean survival time was 4.2 months (range 1-10)., Conclusions: In our experience, full expansion of EsophaCoil was achieved in all cases. This result, was associated with high incidence of retrosternal pain. Relief of dysphagia score was identical to that obtained with other types of Self-Expanding Metal Stent. Coil design prevented tumour ingrowth and allowed retrieval of three migrated stents. Mean survival time was similar to that reported in larger series using different types of Self-Expanding Metal Stent.

Purpose: To evaluate the prognostic value of the DNA repair/redox-protein Ape1/ref-1 in a retrospective series of consecutive non-small cell lung carcinomas (NSCLC)., Patients and Methods: Sections from 91 radically resected NSCLC were analyzed for immunohistochemical expression of Ape1/ref-1. For each case 1,000 tumor cells were evaluated to detect nuclear and cytoplasmic reactivity scored as a percentage of positive cells. With respect to sub-cellular localization and percentage of immunoreactive cells, each tumor was classified as "cytoplasmic" or "non cytoplasmic". The survival rate according to Ape1/ref-1 sub-cellular localization was calculated., Results: The main pattern of Ape1/ref-1 expression was nuclear. No significant difference was observed in Ape1/ref-1 pattern according to histotype (squamous vs adenocarcinoma). Among adenocarcinomas, a cytoplasmic expression of Ape1/ref-1 was significantly associated with poor survival rate in univariate (p=0.01) and multivariate (p=0.07) analyses. In addition, a cytoplasmic expression of the DNA repair protein was also predictive of worse prognosis (log-rank test, p=0.02) in cases with lymph node involvement, regardless of histotype., Conclusion: The results suggest a potential role of Ape1/ref-1 sub-cellular localization as a prognostic indicator in patients with NSCLC. In particular, cytoplasmic localization of the protein seems to confer a poor outcome in subgroups of patients with nodal involvement or adenocarcinoma histotype.

Recent years have witnessed tremendous advances in the fields of pathophysiology, diagnosis and management of hereditary hemochromatosis (HH) and other iron overload syndromes, the dreadful consequences of which are fully preventable by early diagnosis and treatment. Missense mutations in HFE, a newly discovered gene encoding for a major histocompatibility class-I like molecule, have been found to be strictly associated with most cases of HH. The mechanisms by which a dysfunctional HFE molecule determines increased absorption of iron in HH are on the way to be fully clarified, due to the availability of a knockout mouse model. Epidemiologic studies have shown that HH is one of the most common human hereditary disorders. The possibility to identify HFE heterozygotes by means of a simple genetic test have prompted studies on the association between HFE mutations and iron overload syndromes different from HH. In the era of the historic completion of the human genome projects, genetic testing for HH may soon qualify for being adopted in universal population screening policies. In the present paper, the recent advances in the fields of genetics and pathophysiology of HH and other iron overload syndromes will be summarized. Furthermore, its clinical features, pathology and treatment will be reviewed, and the emerging issues of cost-effective diagnosis and of possible population screening strategies will be succintly discussed.

Fatigue is a common complaint of patients with cancer or other physical or mental disorders. In cancer patients, the estimated prevalence of fatigue is high (about 70% to 90% in different surveys). However, despite the high prevalence and widely recognized clinical relevance of fatigue, few studies have been performed to evaluate the putative causal factors and therapeutic approaches for this condition. The paucity of studies has been mainly because of the lack of proper instruments to quantify this clinical problem. Moreover, fatigue is multifactorial, which makes evaluation of precise relationships with other medical conditions difficult. In particular, fatigue is considered the cardinal symptom of anemia. The pathogenesis of anemia-related fatigue remains unclear, but some suggest that abnormalities in energy metabolism play a role in inducing fatigue. In cancer patients, this effect may be exacerbated by the increased metabolic needs associated with tumor growth. At the clinical level, the relationship between anemia and fatigue is universally accepted. However, early studies were unable to show a clear association between fatigue and hemoglobin levels. Recently, new insights were afforded by the implementation of innovative survey instruments that assess the effects of fatigue and other (nonfatigue) symptoms of anemia on the patient's well-being and quality of life. The use of these validated instruments has shown a direct effect of hemoglobin levels on fatigue and other quality of life parameters. Thus, amelioration of anemia and fatigue should be considered a primary endpoint of antineoplastic and supportive-care treatment of cancer patients. Accordingly, the search for new simplified methods of assessment of fatigue and other anemia-related symptoms and their treatment outcomes should be strongly encouraged., (Copyright 2001 by W.B. Saunders Company.)

The prognostic value of combined immunohistochemical analysis for the thyroid transcription factor-1 (TTF-1) and the proliferation marker MIB-1 was assessed in a consecutive series of non-small cell lung carcinomas (NSCLC). Tumor immunoreactivity for TTF-1 and MIB-1 was classified in three groups (-,+,++) and in two groups (-,+), respectively. Comparison across groups for TTF-1 reactivity showed significantly different survival curves (P=0.04). In particular, the best prognosis was associated with a TTF-1 negative pattern, whereas the TTF-1 '++' cases showed the worst prognosis. A trend towards better prognosis was observed for MIB-1 negative cases (P=0.09). Multivariate analysis confirmed independent prognostic significance of TTF-1 (P=0.002), MIB-1 (P=0.01) and pStage (P=0.04). Accordingly, analysing TTF-1 and MIB-1 together, a better prediction of survival was obtained (P=0.02), with the poorest prognosis for the 'TTF-1++/MIB-1+' cases.

Background and Aims: The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the introduction of topical formulations, above all steroids with an hepatic "first pass" devoid of systemic interference. The aim of this study was to evaluate the efficacy and tolerability of Beclomethasone dipropionate (BDP) in a rectal foam formulation, in the treatment of patients suffering from ulcerative colitis., Methods: The experimental protocol took the form of a 28-day open prospective trial using BDP rectal foam in patients suffering from ulcerative colitis. Endoscopic, histological, clinical and tolerability parameters were evaluated. The centres taking part in the trial collected data for 60 cases out of a total of 80 patients enrolled in the study, of both sexes and aged between 20 and 81 years old, suffering from proctosigmoiditis (46.7%) and ulcerative rectocolitis (53.3%)., Results: Endoscopic parameters showed an improvement after 28 days of treatment in 74.5% of patients; a clinical improvement was achieved in 65.2% of cases. In percentage terms of the mean value of all the improved parameters, histological parameters were altered in 56.9% of patients. With regard to tolerability 82% of patients judged the treatment to be good/excellent., Conclusions: In conclusion, in line with recent reports regarding other pharmaceutical forms of BDP, including the use of rectal foam, these data confirm the efficacy and tolerability of this molecule and emphasise the validity of its use in the treatment of ulcerative colitis and proctosigmoiditis.

Thymic carcinomas (primitive malignant epithelial neoplasms of the thymus) are rare tumors which generally remain silent for long periods and rarely metastatize outside the chest. The authors present a case of a 49 year-old patient, with mediastinal mass complicated by pericardial effusion and rapidly extensive liver metastasis. Data in the literature indicate that completeness of the excision at initial operation is the most important prognostic factor, but the presence of necrosis, high number of mitosis and endolymphatic emboli in the specimens could indicate a poor prognosis, suggesting a tempestive treatment and a close follow-up.

We report immediate and late clinical results achieved in 33 patients with achalasia treated with pneumatic dilation as an outpatient procedure. Thirty patients were seen before any therapy and 3 following a failed esophagomyotomy. All patients were submitted to clinical, radiological and manometric evaluation before treatment: six of them belonged to Adams' class I, 19 to class II and 8 to class III. The dilations were performed with Microvasive Regiflex System (30-35-40. mm.). The average number of dilations per patient was 1.4; one dilation was performed in 25 patients, 2 dilations in 6, and three dilation in two. The patients after the dilation were controlled for a maximum period of 3 hours before being discharged from the outpatient facilities. No complications, worthy of note, was related to the procedures. The clinical results were subdivided in four classes according to Vantrappen's schema. Ten days--immediate results--after the first dilation excellent-good results were obtained in 26 patients (78.8%); moderate results in four (12.1%) and poor results in three (9.1%). The mean LES pressure, evaluated in 15 out of 25 cases fell from 37.6 mmHg. Before treatment to a value of 16.2 mmHg after treatment (p < 0.005). Of the 30 patients followed for an average period of 30.6 months (2-82)--late results--excellent-good results were obtained in 24 (80%), moderate results in 4 (13.3%) and poor in 2 (6.7%). In conclusion the clinical results, of our study, repeat those published in a previous prospective evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

The Authors have diagnosed by endoscopy and biopsy 33 primitive gastric lymphomas (6,7% of all malignant gastric tumors diagnosed over 6 years). Endoscopic observation alone diagnosed lymphoma in 63,6% of the cases. Exact diagnosis was made in all cases of polymorphic or multi-ulcerated lesions. The observation of a single ulcerated or ulcero-vegetative lesion (30,3%) suggested diagnosis of carcinoma. A false negative diagnosis of inflammatory pathology was made in 6,1% of the cases. Biopsy gave correct diagnosis in 69,7%. Highest percentage of positive biopsies was obtained in both single and multiple ulcerated lesions (88,2%), while infiltrating lesions provided positive biopsies in 50% of the cases. Endoscopy together with biopsy gave correct diagnosis in 90,9%. In fact, endoscopic diagnosis of lymphoma was confirmed after resection in 7 cases even if the individual biopsies showed superficial gastritis. The Authors believe that correct endoscopic study of primitive gastric lymphomas is based on knowledge of the various morphologies of the tumor and on a systematic performance of a large number of biopsies of both the lesions and surrounding mucosa.