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Background: Cellulite can be seen on the skin in widespread alterations of the skin surface and dimpling. The purpose of this study was to assess the effectiveness and safety of the manual subcision technique to treat dimpling from cellulite, using a specific class IIA medical device (Celluerase)., Methods: The multi-center observational study assessed 200 women treated in a single session for different dimpling, using manual subcision administered by Celluerase. Aesthetic outcomes were evaluated by the authors, and the patients assessed satisfaction levels., Results: Two hundred women between 20 and 55 years were treated. The medical evaluation of patients saw improvements with an average score of 8.1, whereas the subjective evaluation by patients gave an average improvement score of 7.8. Adverse events were reported., Discussion: Women have septa orientation at right angels to the skin surface, and those with cellulite have an irregular septa conformation, with some septa being hypertrophic-thickened, and others being narrowed-lysed. Magnetic resonance imaging has confirmed that cellulite depressions are associated with a significant increase of thickness of underlying subcutaneous fibrous septa. Subcision has immediate results because it eliminates traction on the skin., Conclusion: The study has shown the effectiveness and safety of the manual subcision in the treatment of dimpling. The device used, designed specifically for this technique, has shown itself to be very helpful and effective in terms of practical use, aesthetic outcome and safety, with various advantages compared with other commonly used devices.

Aim: This Italian study evaluated whether painful procedures during the first four weeks of life were related to subsequent weight gain, head circumference (HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated the number of invasive procedures that infants born at less than 32 weeks of gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi Hospital, Florence, from January to December 2015. Weight and HC were recorded at birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler Development - Third Edition., Results: We studied 83 preterm infants with a GA of 28 ± 2 weeks and birth weight of 1098 ± 340 g. A higher number of invasive painful procedures were related to a lower HC standard deviation score at 36 weeks of PMA and six and 12 months of CA and with lower cognitive scores at six months. At 12 months, the relationship only remained significant for infants born at less than 28 weeks (p < 0.001)., Conclusion: Invasive painful procedures affected regular HC growth and short-term cognitive scores in preterm infants in the first year of life., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: We evaluated the outcomes of patients treated with ado-trastuzumab emantasine (T-DM1) after first-line pertuzumab/trastuzumab, compared with those receiving a trastuzumab-only-based regimen., Patients & Methods: Patients who received second-line T-DM1 after pertuzumab/trastuzumab (n = 34) were compared with those who received only trastuzumab (n = 73)., Results: Overall response rate was 33.3% in patients with prior pertuzumab and 57.1% in the remaining subjects. Disease control rate was 47 and 43%, respectively, and the clinical benefit rate was 43.3 and 71.1%, respectively. Median progression-free survival was 5.0 and 11.0 months, respectively (hazard ratio: 2.02; 95% CI: 1.14-3.58; p = 0.01)., Conclusion: Patients treated with T-DM1 who previously received pertuzumab present poorer clinical outcomes compared with those receiving a trastuzumab-only-based regimen in the first-line setting.

The aim of our study was to investigate the relationship between nutritional status (body mass index and phase angle) and psychological symptoms at admission and discharge in a residential population of anorexic patients. We also aimed to determine the evolution of the above psychological symptoms and nutrition rehabilitation from admission to discharge. Thirty-six consecutive patients were included. The evaluation was performed using the following measures at admission and discharge: body mass index, phase angle, Eating Disorders Inventory-3, Multiphasic Personality Inventory-2 and Body Uneasiness. Admission and discharge nutritional status were not correlated with psychometric scores respectively at admission and at discharge. In addition, neither the improvement in the scores on the psychometric scales between admission and discharge was correlated to body mass index, phase angle improvement. For the group as a whole there were significant improvements from admission to discharge in nutritional status, Multiphasic Personality Inventory-2-Depression, Body Uneasiness-Global Score Index and in all the composites of Eating Disorders Inventory-3. Our data showed a disconnection between nutritional status and eating disorders psychopathology and/or psychiatric comorbidities., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: The risk of developing red blood cell (RBC) transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants has recently been emphasized. Our aim was to assess changes in cytokine serum levels after RBC transfusions in a cohort of very preterm infants to evaluate their possible proinflammatory effect., Study Design and Methods: We carried out a prospective observational study. One transfusion event was studied in infants less than 32 weeks' gestation and more than 7 days old (n = 20) admitted to a tertiary neonatal intensive care unit. Interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, interferon-γ (IFN-γ), IL-17, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule serum levels were measured in enrolled patients within 120 minutes before (T 0 ) the RBC transfusion and then within 120 minutes (T 1 ), 12 ± 3 hours (T 2 ), 24 ± 6 hours (T 3 ), and 48 ± 6 hours (T 4 ) after the end of RBC transfusion., Results: Infants received 19.8 ± 3.0 mL of RBCs at the mean age of 50 ± 18 days. Their hematocrit level increased from 24.1 ± 1.2% to 39.4 ± 2.9%. IL-1β, IL-8, IFN-γ, IL-17, MCP-1, IP-10, and ICAM-1 increased significantly after RBC transfusions., Conclusion: Proinflammatory cytokines are increased after RBC transfusion. These findings may contribute to explaining the pathogenesis of TANEC and suggest the opportunity of adopting wise transfusion guidelines that would help to avoid detrimental risks of transfusion-related immunomodulation and of undertransfusion., (© 2017 AABB.)

Objectives  The aim of the study was to compare the effects on cerebral oxygenation in preterm infants of two different procedures for surfactant administration: the LISA (low-invasive method of surfactant administration) and the InSurE (Intubation, SURfactant administration, Extubation). Study Design  Twenty premature infants with respiratory distress syndrome were assigned to receive surfactant either by "LISA" ( n  = 10) or "InSurE" ( n  = 10) procedure. Patients were continuously studied by near-infrared spectroscopy (NIRS) for the measurement of cerebral regional oxygenation (rSO 2 C) and calculation of cerebral fractional oxygen extraction rate (cFTOE), and NIRS data were recorded 30 minutes before ( T 0 ) surfactant administration, during the procedure ( T proc ), and 30 ( T 1 ), 60 ( T 2 T 2 ), and 120 minutes ( T 3 ) afterward. Cerebral blood flow velocity (CBFV) was studied in the anterior cerebral artery at T 0 , T 1 , and T 3 . Results  SpO 2 significantly decreased at T proc in comparison with T 0 , T 1 , T 2 , and T 3 and the decrease was higher in the LISA than in the InSurE group. rSO 2 C was lower at t proc and T 3 in the LISA than in the InSurE group. cFTOE was higher at t proc , t 2 , and t 3 in the LISA group than in the InSurE group. CBFV did not change during the study periods in both groups. Conclusions  The LISA and InSurE procedures transiently decreased rSO 2 C in our population, and the decrease was higher in the LISA group. Consistently, there was a contemporary increase in cFTOE that was higher in the LISA than in the InSurE group, suggesting that it represents a compensatory mechanism., (Georg Thieme Verlag KG Stuttgart · New York.)

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively. In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatinib., Competing Interests: CONFLICTS OF INTEREST The authors have declared no conflicts of interest.

Background: Reconstruction intralipotherapy is a term commonly used in the field of aesthetic medicine, above all in Europe, which defines a specific injection technique developed for the treatment of localized fat with substances that provoke the lysis of adipocytes by means of an injection directly into the adipose tissue with a long needle. The aim of this study is to define the technique in detail and everything that is associated with it, on the basis of years of multicenter experience by doctors who perform it., Materials and Methods: From January 2010 to December 2014, 3,080 European physicians were trained in intralipotherapy technique, and approximately 152,500 patients were treated. The adipocytolytic agent used is a Conformité Européene-certified device. The technique, equipment, protocol, posology, postoperative management, and adverse events are described below., Results: The intralipotherapy technique combined with the appropriate adipocytolytic agent has been shown to be effective in every zone on the average of 76.7% of the cases. The variability is due to the area treated and the patient. The standardization of the technique, homogeneity of the protocol, and the posttreatment management have been essential for standardizing the results and minimizing any adverse events. The latter occurred only in a small percentage of the cases, while those more serious have been extremely rare., Conclusion: This study shows how the intralipotherapic technique, when performed properly with an appropriate adipocytolytic device and when proper precautions are taken, can be effective and safe for reducing undesirable subcutaneous fat deposits.

Background: There are no validated predictive markers for lapatinib and capecitabine in patients with trastuzumab-resistant HER2 positive metastatic breast cancer., Methods: Data of 148 consecutive patients treated with lapatinib and capecitabine from March 2007 to December 2013 were collected from 13 Italian institutions. Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with logrank test. The association of clinicopathological variables and the outcome was studied by binary logistic regression analysis and Cox proportional hazard analysis., Results: At a median follow-up of 41 months, median PFS and OS were 7 and 21 months, respectively. Patents with a PFS longer than 7 months had a significantly longer OS, compared with patients with a PFS equal to or shorter than 7 months (36 vs 15 months; p<0.001). Multivariate analysis revealed the benefit of lapatinib-based therapy in terms of PFS and OS was significantly associated with time-to-progression (TTP) on prior first-line trastuzumab-based therapy. In particular, each additional month on first-line trastuzumab based therapy was associated with a reduction in hazard of progression and death after the initiation of lapatinib-based therapy of 2% and 4%, respectively., Conclusions: A longer TTP to first line trastuzumab seems to predict a prolonged PFS and OS with subsequent lapatinib and capecitabine.

Background: The State-Trait Anger Expression Inventory 2 (STAXI-2) is a psychometric instrument measuring anger experience and expression. Associations between the STAXI-2 and risk of breast cancer (BC) are rarely considered together in a prospective study., Patients and Methods: A total of 117 women with breast symptoms referred for breast examination were selected and assessed before any diagnostic procedures., Results: Twenty-four patients with BC, 44 with benign breast disease (BBD) and 49 healthy individuals (HHS) were included. Scores for parameters state anger/feel like expressing anger physically (SANGP) were significantly higher in the HHS group (HHS vs. BBD: p=0.027; HHS vs. BC: p=0.025). BC patients showed a trend to lower scores in almost all scales of STAXI-2, except for the scales trait anger/angry temperament (TANGT), anger expression-in (AX-I), and anger control-out (AC-O), that were higher than the two other groups' scores., Conclusion: The results of this study do not support a specific link between STAXI-2 and breast cancer risk., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Gastric cancer is one of the most common cancers worldwilde. The five-year survival for stage IV gastric cancer is around 5-10% in Western countries. Advanced gastric cancer is sensitive to numerous agents, but there is no generally accepted standard regimen. Here we report on a case of advanced gastric cancer occurring in a 72-year-old man who underwent treatment with capecitabine plus oxaliplatin, achieving a complete response.

The purpose of this study was to analyze the differences in standing balance during dominant and nondominant one-legged stance among athletes of different sports and sedentary subjects. The right-footed subjects of four groups (sedentary, n = 20; soccer, n = 20; basketball, n = 20; windsurfer n = 20) underwent 5-sec unipedal (left and right foot) stabilometric analysis with open eyes and closed eyes to measure center of pressure (COP) sway path and COP velocity (mean value, anteroposterior, and laterolateral in millimeters per second). The soccer group showed better standing balance on the left leg than the sedentary group (P < 0.05). No other significant differences were observed within and amongst groups. The soccer players have a better standing balance on the nondominant leg because of soccer activity.

Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active anthracycline directly to the tumor site, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. Recently, a regimen in which paclitaxel is infused weekly over 1 h produced substantial antitumor activity with little myelosuppression. We designed a phase II trial to study the efficacy and toxicity of 10 mg/m(2) PLD on Days 1, 8 and 15, plus 70 mg/m(2) paclitaxel weekly in patients with untreated metastatic breast cancer and a high risk of cardiotoxicity. The study included 35 patients, with 31 (88.5%) evaluable for efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more sites of disease. Overall, 4 complete and 16 partial responses were noted with an overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive disease. Toxicity was found to be manageable in that the only grade 3-4 side effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%; leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was observed. In conclusion, weekly PLD plus paclitaxel appears to be a well-tolerated and effective approach for metastatic breast cancer patients with a high risk of cardiotoxicity.

Aims and Background: Patients with metastatic breast cancer previously treated with anthracyclines for advanced disease are usually refractory to any further treatment with anthracyclines and have a poor prognosis. Therefore, new drugs or new combinations of drugs are needed. One approach has been to focus on the type of chemotherapy with low toxicity that preserves quality of life during treatment, such as weekly drug administration., Study Design: We designed a dose-finding study to determine the maximum tolerated dose of gemcitabine plus docetaxel, given on a weekly schedule in metastatic breast cancer previously treated with anthracyclines. Three escalating doses of gemcitabine (900, 1000 and 1100 mg/m2) on days 1 and 8 in combination with a fixed dose of docetaxel, 35 mg/m2 on days 1 and 8 were planned. Dose-limiting toxicity included grade > 3 hematologic toxicity, grade > 2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if 1 out of 3 patients at any dose level experienced dose-limiting toxicity., Results: Nine patients received a mean of 5.1 (range, 1-9) cycles. Gastrointestinal and leukopenia were the main dose-limiting toxicity. No patient experienced dose-limiting toxicity at dose level 1; at dose level 2, 2 out of 3 patients had dose-limiting toxicity and 3 additional patients treated at dose level 2 confirmed that the maximum tolerated dose had been reached., Conclusions: The recommended gemcitabine dose in combination with docetaxel (35 mg/m2 for a phase II study) was established at 900 mg/m2.

Botryosphaeria rhodina DABAC P82 and Pleurotus pulmonarius CBS 664.97 were tested for their ability to grow and to degrade aromatic hydrocarbons in an aged contaminated soil. To evaluate the impact of indigenous microflora on the overall process, incubations were performed on both fumigated and nonfumigated soils. Fungal colonization by B. rhodina was unexpectedly lower in the fumigated than in the nonfumigated soil while the growth of P. pulmonarius showed an opposite response. Degradation performances and detoxification by both fungi in the nonfumigated soil were markedly higher than those observed in the fumigated one. Heterotrophic bacterial counts in nonfumigated soil augmented with either B. rhodina or P. pulmonarius were significantly higher than those of the corresponding incubation control (6.7 +/- 0.3 x 10(8) and 8.35 +/- 0.6 x 10(8), respectively, vs 9.2 +/- 0.3 x 10(7)). Bacterial communities of both incubation controls and fungal-augmented soil were compared by numerical analysis of denaturing gradient gel electrophoresis profiles of polymerase chain reaction (PCR)-amplified 16S ribosomal RNA (rRNA) genes and cloning and sequencing of PCR-amplified 16S rRNA genes. Besides increasing overall diversity, fungal augmentation led to considerable qualitative differences with respect to the pristine soil.

Contaminated soil from a historical industrial site and containing sulfide ore ashes and aromatic hydrocarbons underwent sequential leaching by 0.5 M citrate and microbial treatments. Heavy metals leaching was with the following efficiency scale: Cu (58.7%) > Pb (55.1%) > Zn (44.5%) > Cd (42.9%) > Cr (26.4%) > Ni (17.7%) > Co (14.0%) > As (12.4%) > Fe (5.3%) > Hg (1.1%) and was accompanied by concomitant removal of organic contaminants (about 13%). Leached metals were concentrated into an iron gel, produced during ferric citrate fermentation by the metal-resistant strain BAS-10 of Klebsiella oxytoca. Concomitantly, the acidic leached soil was bioaugmented with Allescheriella sp. DABAC 1, Stachybotrys sp. DABAC 3, Phlebia sp. DABAC 9, Pleurotus pulmonarius CBS 664.97, and Botryosphaeria rhodina DABAC P82. B. rhodina was most effective, leading to a significant depletion of the most abundant contaminants, including 7-H-benz[DE]anthracene-7-one, 9,10-anthracene dione and dichloroaniline isomers, and to a marked detoxification as assessed by the mortality test with the Collembola Folsomia candida Willem. The overall degradation activities of B. rhodina and P. pulmonarius appeared to be significantly enhanced by the preliminary metal removal.

Objective: A phase II study was performed to evaluate efficacy and safety of the combination vinorelbine and docetaxel in patients with metastatic breast cancer previously treated with anthracycline-based regimens. Overall 41 patients were included in the study., Methods: Treatment consisted of vinorelbine 25 mg/m2 and docetaxel 75 mg/m2, both administered on day 1 every 3 weeks for a maximum of 9 cycles. Most patients (92%) were postmenopausal with a median age of 57 years, and median ECOG performance of 1. Sites of disease were viscera in 42% of patients, bones in 30%, soft-tissues in 32%. Sixty-five percent of patients had >2 metastatic sites. Previous treatments included neo-adjuvant chemotherapy in 7.3% of cases, adjuvant chemotherapy in 71%, and front-line chemotherapy for advanced disease in 50% of cases., Results: A total of 273 cycles of chemotherapy were delivered (mean 6 cycles/patient). All patients were assessable for toxicity: alopecia was recorded in all patients, grade 2-3 neutropenia in 34% and grade 4 in 9.7%; grade 2-3 nausea/vomiting in 29%, grade 2-3 mucositis in 24.3%. Out of 39 patients evaluable for response, 7 (18%) complete responses and 13 (33%) partial responses have been recorded with an overall response rate of 51%. Six patients (15%) experienced stable disease and 13 patients (33%) progressed. Mean duration of responses was 15.2 months. Median time to progression and median overall survival were 6.2 and 14 months, respectively., Conclusion: In patients with metastatic breast cancer previously treated with anthracyclines the combination vinorelbine-docetaxel is very active and well tolerated representing a valid therapeutic option for the management of this patient population.

Background: This study was designed to evaluate the efficacy and safety of irinotecan/cetuximab administered as third- or fourth-line therapy in a retrospective series of patients with metastatic colorectal cancer refractory to oxaliplatin and irinotecan., Patients and Methods: Most patients (90%) had been previously treated with adjuvant 5-fluorouracil/leucovorin, and all had received oxaliplatin-based regimens before receiving irinotecan-based second-line treatment. Sixty patients with irinotecan-refractory colorectal cancer received a regimen comprising weekly irinotecan 120 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for the subsequent administrations. A single treatment cycle comprised 4 weekly infusions followed by 2 weeks of rest., Results: According to an intent-to-treat analysis, a partial response was exhibited in 12 of 60 enrolled patients (20%; 95% confidence interval, 11%-32%) with a median duration of 5.1 months (range, 3-7.4 months). The tumor growth control rate was 50% (95% confidence interval, 37%-63%). Objective responses did not correlate with performance status, number of sites of disease, and pretreatments or epidermal growth factor receptor status. The median progression-free survival was 3.1 months (range, 1.2-9 months), whereas median overall survival was 6 months (range, 2-13 months). Both survival parameters correlated with performance status at the beginning of treatment. The main grade 3/4 toxicities were nausea (33%), diarrhea (27%), leukopenia (18%), asthenia (13%), and acne-like reaction (13%)., Conclusion: Our data suggest that the weekly irinotecan/cetuximab regimen is feasible in an outpatient setting and tolerated by most patients. At present, combinations of chemotherapy with cetuximab are being evaluated in patients with earlier-stage disease in a number of ongoing studies.

Purpose: We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer., Patients and Methods: A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2 regimen)., Results: One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed., Conclusion: There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

Phanerochaete chrysosporium NRRL 6361 and Pleurotus pulmonarius CBS 664.97 were tested for their ability to grow under nonsterile conditions and to degrade various aromatic hydrocarbons in an aged contaminated soil that also contained high concentrations of heavy metals. After 24 days fungal incubation, carbon-CO2 liberated, an indicator of microbial activity, reached a plateau. At the end of the incubation time (30 days), fungal colonization was clearly visible and was confirmed by ergosterol and cell organic carbon determinations. In spite of unfavorable pH (around 7.4) and the presence of heavy metals, both fungi produced Mn-peroxidase activity. In contrast, laccase and aryl-alcohol oxidase were detected only in the soil treated with P. pulmonarius CBS 664.97 and lignin-peroxidase in that with P. chrysosporium NRRL 6361. No lignin-modifying enzyme activities were present in non-inoculated soil incubated for 30 days (control microcosm). Regardless of the fungus employed, a total removal of naphtalene, tetrachlorobenzene, and dichloroaniline isomers, diphenylether and N-phenyl-1-naphtalenamine, was observed. Significant release of chloride ions was also observed in fungal-treated soil, in comparison with that recorded in the control microcosm. Both fungi led to a significant decrease in soil toxicity, as assessed using two different soil contact assays, including the Lepidium sativum L. germination test and the Collembola mortality test., (Copyright (c) 2005 Wiley Periodicals, Inc.)

Background: This study evaluated the antitumor efficacy and safety of a novel oxaliplatin/raltitrexed combination in pretreated advanced colorectal cancer patients., Patients and Methods: Forty-five patients with 5-fluorouracil-refractory metastatic colorectal cancer received raltitrexed 3.0 mg/m2 as a 15-minute intravenous (i.v.) infusion, followed 45 min later by l-OHP 130 mg/m2 i.v. as 2-h venous infusion on 1 day every 3 weeks. All patients had histologically proven metastatic colorectal cancer, age 18-75, measurable disease and normal baseline biological values. Most patients (60%) had >2 disease sites. All patients were assessed for safety and also for response according to an intent-to-treat fashion., Results: The overall response rate was 29% (95% CL 16%-44%) including one CR (2%) and 12 PR (27%). Six patients (16%) showed a stabilization of disease for a tumor growth control rate of 45%. The median time to progression was 4 months (range 1-12+) and median overall survival was 9 months (range 1-29+)., Conclusion: These data confirm that this oxaliplatin/raltitrexed combination is effective against metastatic colorectal carcinoma, well tolerated with low grade toxicity and easy to administer. Further evaluation of this regimen seems warranted as an alternative to fluoropyrimidine-based combinations.

We studied a consecutive series of 95 patients undergoing radical surgical resection of lower lip squamous cell carcinoma (LLSCC) to assess the correlation between lymph node status and several prognostic variables, such as sex and age, tumour size, histologic grading, maximal microscopic tumour thickness, perineural infiltration and p27Kip1 protein status, to see which of these might be predictive of the development of lymph node metastases. Statistical analysis demonstrated a significant association between node status and tumour size, histological grading, maximal thickness, perineural invasion and p27Kip1 protein expression; additionally to node metastasis, low p27Kip1 protein expression was significant correlated with high microscopic thickness. These results indicate that lower lip squamous cell carcinomas of >2 cm, with G3-G4 histological grading, maximal thickness of >6 mm, perineural invasion and low p27Kip1 protein expression (LI<19.7%) are at high risk for the development of lymph node metastases.

Objective: To evaluate the prognostic utility of argyrophilic nucleolar organizer region (AgNOR) protein parameters and Ki-67-immunostained growth fraction (Ki-67 labelling index) and to correlate AgNORs with Ki-67 LI and the main clinicopathologic parameters in gastrointestinal stromal tumors (GISTs)., Study Design: On 55 patients with surgically excised GISTs, visualization and quantification of AgNORs were performed as specified in the guidelines of the Committee on AgNOR Quantification., Results: AgNOR protein area (NORA) > or = 5.28 microns 2 was statistically associated with mitotic rate > or = 5 x 10 high-power fields (hpfs) (P < .001) and presence of necrosis (P < .001); Ki-67 LI > or = 9.69% was significantly associated with mitotic rate > or = 5 x 10 hpfs (P < .001), size > or = 5 cm (P = .033) and presence of necrosis (P < .001). Ki-67 LI and NORA strongly correlated. Preliminary Kaplan-Meier survival analysis showed that an increased value of NORA, Ki-67 LI, mitotic rate, tumor size and presence of necrosis had a negative influence on patient survival. Multivariate regression analysis showed that only NORA and Ki-67 LI were independent parameters in predicting the clinical outcome for patients with GISTs. Mitotic rate and necrosis remained as independent prognostic factors when NORA and Ki-67 LI were not allowed to enter in models., Conclusion: AgNOR protein quantity, as determined by image cytometry, and Ki-67 immunostaining seem to represent reliable predictive parameters in GISTs and are independent of mitotic rate, tumor dimension and necrosis.

Fifty-eight patients with metastatic breast cancer were randomly treated with a combination of cyclophosphamide 500 mg/m2 on days 1 and 2 plus epidoxorubicin 90 mg/m2 on day 1 every 3 weeks (group A = 18 patients), or paclitaxel 175 mg/m2 cycle plus doxorubicin 50 mg/m2/cycle every 3 weeks (group B = 20 patients), or paclitaxel as above plus epidoxorubicin 90 mg/m2/cycle every 21 days (group C = 20 patients). The trial was designed as a randomized, multi-institutional phase II study where the cyclophosphamide/epidoxorubicin regimen represented the calibration arm. The overall response rate was 50% (95% CL 26-74%) for arm A, 65% (95% CL 41-85%) for arm B and 70% (95% CL 46-88%) for arm C. The complete response rate was 6% for arm A, 10% for arm B and 15% for arm C. Although this trial was non comparative, the median duration of response and median overall survival were almost superimposable in all arms. The taxane-based regimens were associated with significant neurotoxicity in nearly 20% of cases, while febrile neutropenia represented the most severe side-effect. Our data suggest that the anthracycline/taxane combinations are more effective than the epidoxorubicin/cyclophosphamide regimen, at least in terms of objective response rates. These regimens may represent the treatment of choice when oncologists are faced with aggressive visceral metastatic breast cancer in non elderly women.

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following variables were investigated: tumor size, histologic grading, tumor maximal thickness, perineural infiltration and DNA ploidy, in a group of patients undergoing surgical treatment for LLSCC, and to show which of these might be predictive of the development of lymph node metastases.

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following factors were investigated: tumor size, histologic grading maximal thickness, perineural invasion, DNA ploidy and PCNA expression. In conclusion, we found that LLSCC greater than 2 cm in diameter, with histological grading G3-G4, thickness of more than 6 mm, DNA aneuploidy and high PCNA expression (PCNA LI > 0.48), were at high risk for the development of lymph node metastases.

Biological agents might offer various therapeutic opportunities in the treatment of cancer, including a direct and/or host-mediated antiproliferative effect and also the possibility to favorably modulate tumor resistance to antineoplastic drugs. We studied the in vitro antiproliferative effects of interferon (IFN)-gamma on the mouse B16 melanoma and Friend erythroleukemia, and the human K562 erythroleukemia, as doxorubicin (DXR)-sensitive and -resistant (multidrug resistant) variants. These effects were marked in B16 melanoma and rather slight in K562 erythroleukemia, without any difference between the DXR-sensitive and -resistant lines. The chemosensitive variant of Friend erythroleukemia showed an intermediate response, which was greater than that seen in its resistant counterpart. There was no apparent relationship between the antiproliferative activity of IFN-gamma and the glutathione content of the cell lines. On the other hand, this activity was enhanced by co-treatment with glutathione-depleting concentrations of buthionine sulfoximine, but only in the cell lines which had responded better to IFN-gamma alone. This result probably confirms that a free radical mechanism plays a part in the antitumor effect of the cytokine. Finally, a range of concentrations of IFN-gamma, including slightly cytotoxic ones, did not substantially improve the antiproliferative effects of doxorubicin on the various cell lines, except in the DXR-sensitive variant of Friend erythroleukemia where a synergistic effect of the combination was observed. Thus, our results are not very promising with regard to a possible favorable modulatory activity by IFN-gamma of DXR (multidrug)-resistance.

Forty-seven women affected by Stage Ic-IV epithelial carcinoma of the ovary were treated with the combination of cisplatin, adriamycin (40-50 mg/m2 day 1), and cyclophosphamide (800 mg/m2 day 1) (CAP). Two different schedules of cisplatin were used: 20 mg/m2 day 1-->5 (CAP 5), or 80 mg/m2 on day 1 (CAP 1). In the group of patients with measurable disease the overall response rate was 52%, with a 19% complete response rate. The mean disease-free survival of patients without measurable disease was 24.0+ months. The mean survival of the whole group was 29.2+ months. The mean survival of patients with measurable disease and those without measurable disease was 21.7+ and 35.0+ months respectively. The schedule of cisplatin employed did not influence disease-free survival since the difference between the CAP 1 (21+ months) and the CAP 5 (25+ months) groups was not statistically significant. However the CAP 5 schedule seemed to be better tolerated since it of allowed the delivery be 99% of the planned dose of CDDP, while in the CAP 1 group the dose of CDDP given was only 74% of that planned.

Taking into account the possible regulatory influences of the beta-adrenergic system on lymphocyte proliferation as well as the proposed role of cyclic 3'-5'-adenosine monophosphate (cAMP) in the modulation of multidrug resistance (MDR) in tumour cells, we have tried to assess the status of the interactions between the beta-adrenergic system and a mouse lymphocytic leukemia, the P388, both as a doxorubicin-sensitive (P388) and -resistant (MDR) variant (P388/DXR). P388 showed a low total number of high affinity 125I-pindolol binding sites (340 +/- 33/cell, Kd 108 pM) when compared with normal splenocytes (1221 +/- 67 sites/cell, Kd 97 pM). The number of beta-adrenergic receptors was even lower in P388/DXR cells (230 +/- 41 sites/cell, Kd 101 pM). In addition, these receptors were subnormally expressed on the cell surface: only 26% and 52% of the total receptors were surface receptors in P388 and P388/DXR, respectively, whereas it was 87% in normal splenocytes. Isoproterenol slightly (less than 1-fold) stimulated cAMP accumulation in P388 and P388/DXR; the stimulation observed in splenocytes was 2.5-fold. In addition, the basal levels of cAMP appeared to be low (0.48 +/- 0.05 pmoles/10(6) cells in P388 and 0.71 +/- 0.08 pmoles/10(6) cells in P388/DXR; 3.47 +/- 0.28 pmoles/10(6) cells in splenocytes) in the two leukemias and they were only slightly (less than 2-fold) increased by forskolin, which otherwise stimulated about 15-fold cAMP accumulation in splenocytes; thus, P388 and P388/DXR were probably also defective in their adenylate cyclase activity. It can be concluded that, owing to multifactorial mechanisms, the lymphocytic leukemia P388, also as an MDR variant, is minimally sensitive to the direct influences of the beta-adrenergic system, probably including any effect of this system on drug-sensitivity.