Search

Objective: In the present phase II study, we evaluated the efficacy and safety of a docetaxel-oxaliplatin-capecitabine combination as a first-line treatment in patients with advanced gastric cancer. Patients and Methods: A total of 27 patients (18 males) with histologically confirmed inoperable gastric adenocarcinoma were recruited. Docetaxel was given (50 mg/m2 i.v.) on day 1 followed by oxaliplatin (75 mg/m2 i.v.) also on day 1. Capecitabine (2,750 mg/m2) was given orally as two daily divided doses from days 1 to 7. Cycles were repeated every 2 weeks. All patients had measurable disease and 18 of them had a performance status (WHO) of 0. Results: A total of 240 treatment cycles were administered. All patients were evaluable for toxicity. Four patients who discontinued treatment early (having received only 3 chemotherapy cycles) were included as non-responders in an intention-to-treat response analysis. Complete response, partial response, stable disease and progressive disease were observed in 4 (15%), 12 (44%), 3 (11%) and 8 (30%) patients, respectively. The observed response rate was 59%, and the disease control rate (complete response + partial response + stable disease) was 70%. At the time of analysis, 6 patients were still alive and the median survival was 18.0 months. The most common grade III/IV toxicities observed were neutropenia (5%), diarrhea (2%), palmar-plantar erythrodysesthesia (2%) and neurotoxicity (1%). All other toxicities were mostly of grade I/II and easily manageable. Conclusion: The combination of docetaxel, oxaliplatin and capecitabine in the described mode of administration represents a relatively active and well-tolerated regimen in patients with advanced gastric cancer and warrants further evaluation. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The corticotropin-releasing hormone (CRH) system, consisting of CRH, urocortins (Ucns), their receptors CRH1 and CRH2, and CRH-binding protein, holds the principal role in mediating the response to stress stimuli. Besides their expression in the brain, CRH neuropeptides and receptors have been found in multiple peripheral sites. We investigated the expression of the CRH system in the human liver, using RT-PCR and immunohistochemistry. Ucn 1 gene transcripts were amplified in all the human liver biopsies examined. Ucn 1 immunoreactivity was localized in hepatocytes. CRH1 and CRH2(α) receptor gene expression was also found, and receptor protein had a similar distribution to Ucn 1. Finally, Ucn 1 and CRH receptor expression was demonstrated in hepatic biopsies from a variety of liver pathologies, including primary or metastatic liver carcinoma and cirrhosis. We conclude that the CRH system is expressed by human liver under normal and pathological conditions, Ucn 1 being the major ligand. Further study is required to unfold the biological role of these effectors in liver physiology and pathogenesis, as they may act in an autocrine manner through activation of the CRH receptors expressed locally. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Pegylated liposomal doxorubicin (PLD) and capecitabine (CAP) have separately shown significant antitumor activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors. Patients and Methods: Fifteen patients with histologically confirmed inoperable solid neoplasms were enrolled. The patients’ median age was 65 years, 10 were male, and 12 had a performance status score (WHO) of 0–1. PLD was administered on day 1 as a 1-hour intravenous infusion at escalated doses ranging from 35 to 40 mg/m2. CAP was administered on days 1–14 per os, at escalated doses ranging from 1,600 to 1,800 mg/m2, given as two daily divided doses. Treatment was repeated every 3 weeks. Results: At the dose of PLD 40 mg/m2 and CAP 1,800 mg/m2, all 3 enrolled patients presented DLTs [2 patients grade 3 palmar-plantar erythrodysesthesia (PPE) and 1 patient grade 3 asthenia] and thus, the recommended MTD for future phase II studies is PLD 40 mg/m2 and CAP 1,700 mg/m2. A total of 57 treatment cycles were administered. Grade 2/3 neutropenia complicated 9 (17%) cycles and 1 patient was hospitalized for febrile neutropenia. There was no septic death. The main nonhematologic toxicity was PPE grade 2 in 3 (19%) patients and grade 3 in 4 (27%). PPE was the reason of treatment interruption for 3 patients. Other toxicities were mild and easily manageable. Two patients (16%) with partial response suffering from gastric cancer and 5 patients with (42%) stable disease were observed among 12 evaluable patients. Conclusions: The results of this phase I study demonstrate that PLD and CAP can be combined at clinically effective and relevant doses. However, PPE is a common side effect and further investigation is warranted to define its precise role in the treatment of solid malignancies. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The degree of penetration of clarithromycin into the pleural fluid has not been studied. Objective: To determine the degree to which clarithromycin penetrates into empyemic pleural fluid using a new rabbit model of empyema. Methods: An empyema was created via the intrapleural injection of 1 ml turpentine followed 24 h later by instillation of 5 ml (1010) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, clarithromycin 30 mg/kg was administered intravenously. Antibiotic levels were determined on samples of pleural fluid and blood samples collected serially over 12 h. Antibiotic levels were estimated using HPLC. Results: The antibiotic penetrated well into the empyemic pleural fluid (AUCPF/AUCserum ratio of 1.57). The time to equilibration between the pleural fluid and blood antibiotic levels was 8 h. The peak pleural fluid level (CmaxPF of 2.88 μg/ml) occurred 1 h (TmaxPF of 1 h) after infusion and decreased thereafter. The Cmaxserum was 3.53 μg/ml at 1 h after administration. Conclusion: The levels of clarithromycin in the pleural fluid after intravenous administration are inhibitory for most of the usual pathogens causing empyema. The degree of penetration of clarithromycin should be considered when macrolides are selected for the treatment of patients with empyema. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder characterized by pancytopenia, hemolysis, and thrombosis. Abdominal vein thrombosis is a life-threatening manifestation of this disease. We present a patient with complete spleen necrosis due to thrombosis of the splenic vessels. After splenectomy, other causes of thrombophilia were excluded and the diagnosis of PNH was established. The patient was put on anticoagulation but despite the prophylactic international normalized ratio maintained over the last 18 months of follow-up, he had another episode of intrahepatic thrombosis which was treated with tissue plasminogen activator thrombolysis. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Wound healing relies on a coordinated expression and release of growth factors controlling angiogenesis. We measured vascular endothelial growth factor (VEGF) levels in serum and early wound fluid following primary sutured and mesh repair of abdominal hernias. Materials and Methods: Thirty-seven patients were studied measuring serum and wound drainage fluid VEGF by enzyme-linked immunosorbent assay preoperatively and on the 1st, 3rd, 5th and 7th postoperative days. Results: Serum and wound fluid VEGF levels increased significantly by the 3rd postoperative day and continued to rise during the conduct of the study with wound fluid concentrations always exceeding serum levels. The kinetics of VEGF increases were similar in both types of hernia repair; however, serum and wound levels rose slightly earlier in the mesh repair group. Conclusions: Steadily increasing levels of VEGF are detected during the early proliferative phase of wound healing in both serum and wound fluid. It is unknown whether either is predictive for delayed hernia recurrence.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The associations between serum β-endorphin levels and clinical and metabolic variables as well as β-endorphin changes after surgically induced weight loss were investigated in 43 morbidly obese patients. A significant positive correlation between β-endorphin and body weight, degree of body weight increase and ACTH was found preoperatively. Only body weight was independently associated with β-endorphin levels. Twelve months following vertical banded gastroplasty, there was an extensive weight loss in all patients and improvement in their metabolic profile. A significant reduction in β-endorphin levels which was proportional to the extent of weight loss was also observed. [ABSTRACT FROM AUTHOR]

Serum sex hormone levels were measured preoperatively in 57 morbidly obese patients (19 men and 38 premenopausal women) and 12 months after vertical banded gastroplasty. In the male group, there was a significant decrease in estradiol and an increase in follicle-stimulating hormone (FSH), total testosterone and sex-hormone-binding globulin (SHBG). Among female patients, a significant decrease in estradiol, total and free testosterone and an increase in FSH and SHBG was found. Irregular menses present preoperatively in 5 women were corrected after successful weight loss. In conclusion, altered sex hormonal levels and gynecologic abnormalities associated with morbid obesity are corrected with adequate weight loss following vertical banded gastroplasty. [ABSTRACT FROM AUTHOR]

Using an ELISA method, the sera of 43 patients with colon adenocarcinoma (CA) and of 26 surgical patients with nonmalignant disease of the gastrointestinal tract were studied for the presence of autoantibodies against cardiolipin (CLP) before and 1 month after surgery. Forty healthy volunteers were used as controls. Fourteen CA patients were found to be positive for anti-CLP autoantibodies before surgical treatment, and 15 patients were found to be positive 1 month after surgery. The difference between the group of CA patients and either the group of patients with nonmalignant diseases of the GI tract, or the group of healthy individuals was statistically significant (p = 0.003). The group of CA patients with high anti-CLP serum titer had a better outcome compared with the group of patients without detectable autoantibody titer (p = 0.08), estimated based on the frequency of recurrences, during the follow-up period. Further studies are in progress to evaluate the significance of anti-CLP antibodies as a biological marker of prognosis in CA patients. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to an article about laparoscopic cholecystectomy.