Viral hepatitis, HIV, human herpes virus and Treponema pallidum infection in haemodialysis patients from Kosovo, 2005.

The serological status of hepatitis viruses and other infectious diseases in the 66 dialysed patients of one haemodialysis unit in Kosovo were studied, comparing the data with a large group of blood donors and out-patients. All dialysed patients were hepatitis A virus (HAV) positive. Prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (anti-HBs), and hepatitis B core antibodies (anti-HBc) was 14 of 66, 21% (95% confidence interval (CI): 12-33%), 5 of 66, 8% (95%CI: 5-22%), and 50 of 66, 76% (95%CI: 64-85%), respectively. Antibodies to hepatitis C virus (anti-HCV) prevalence was 57 of 66, 86% (95%CI: 76-94%). No human immunodeficiency virus (HIV) positive case was found. Prevalence of past herpes simplex virus type 2 (HSV-2) infection was 29% (95%CI: 18-41%). Two patients (3%, 95%CI: 0-10%) were positive for Treponema pallidum and 18% (95%CI: 10-30%) were human herpesvirus 8 (HHV-8) antibody positive. Four hundred and fifty-two subjects were recruited for comparison. Markers of past HAV infection was associated with haemodialysis (Fisher s exact test p-value=0.037). Dialysed patients were at a higher risk of being HBsAg positive than others: the sex- and age-adjusted odds ratio (OR) was 5.18 (95%CI: 1.87-14.32). Anti-HBc positivity was strongly associated with haemodialysis: the sex- and age-adjusted OR was 6.43 (95%CI: 3.22-12-85). Anti-HCV positivity was 86% and 1% in presence and absence of haemodialysis, respectively. The Fisher s exact test for association proved a strong association between haemodialysis and HCV (p-value<0.0001). The OR for association between haemodialysis and HSV-2 positivity was 3.20 (95%CI: 1.46-7.00). Significant associations were also observed between haemodialysis status and antibodies to Treponema pallidum (Fisher s exact test p-value=0.044). In Kosovo, the prevalence of viral hepatitis infection and other viral infections and Treponema pallidum among dialysed patients is high, indicating major ongoing nosocomial transmission.

Helicobacter pylori seroprevalence in selected groups of Albanian volunteers.

BACKGROUND: Albania is a Mediterranean, South-East European developing country where epidemiological data on infectious diseases are scarce. In this study, the seroprevalence of Helicobacter pylori infection in 1,088 Albanian healthy volunteers (472 females followed-up to a prenatal clinic, 173 recruits, 443 health care workers) was evaluated. MATERIALS AND METHODS: Sera were tested for immunoglobulin-G (IgG) antibodies against H. pylori using a quantitative enzyme immunosorbent assay. RESULTS: The overall H. pylori seroprevalence was 70.7%. The H. pylori seroprevalence increased by age, from 60.4% in individuals younger than 20 years to 81% among those > or = 50 years of age with a significant trend of increase by age. The overall seroprevalence was 73.9% for females and 59.5% for males. In addition the seroprevalence was 55.3% for people living in rural areas and 72.3% for people living in urban areas. No significant differences were found according to level of education except for individuals with elementary level of education. Nurses and hospital auxiliaries have significantly higher H. pylori seroprevalence when compared to other health care workers (physicians and office workers). When each variable (age, gender, area of residence, occupation, and education level) was adjusted for the confounding effect of the other variables by stepwise logistic analysis, we observed that age greater than 40 years and female gender remain the only variables independently associated with the presence of H. pylori IgG antibodies. CONCLUSIONS: H. pylori is highly prevalent among the Albanian population. Improving living conditions, education in hygiene, and the supply of running water are measures to prevent the transmission of H. pylori infection and other infections spread by the fecal-oral route in Albania.

Hepatitis B virus infection in health care workers in Albania: a country still highly endemic for HBV infection.

BACKGROUND: Health care workers (HCW) have an elevated risk of acquiring and transmitting parenteral infections. The aim of this study was to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers with the final goal to encourage HBV vaccination of the non-immune Albanian HCW. METHODS: Among 480 HCW enrolled, 92 were physicians, 246 were nurses/techniques, 120 were auxiliary workers and 22 were office workers. RESULTS: The HBsAg, anti-HBc and anti-HCV prevalence were 8.1%, 70% and 0.6%, respectively. The highest (11.4%) HBsAg prevalence was observed in the youngest age group (20-30 years of age). High HBsAg prevalence (7.2-7.5%) was detected also in age groups above 30 years. The highest HBsAg prevalence (12.6%) was found in the auxiliaries. The anti-HBc prevalence increased significantly with age from 59% in HCWs younger than 39 years to 87% among those older than 50 years. After adjustments for different job categories, age older than 40 years remained independently associated with anti-HBc positivity (OR = 2.9; 95% CI 1.9-4.6) and inversely associated with the lack of HBV immunity or infection markers (OR = 0.4; 95% CI 0.2-0.7). Of 142 HBsAg negative and/or anti-HBc Ab negative sera, 28 (20%) tested positive for anti-HBs. The 114 remaining individuals with no HBV infection or immunity markers were vaccinated against HBV infection. CONCLUSIONS: A high HBV infection rate and low HBV vaccination coverage were found in Albanian HCW. Albania is a Mediterranean country still highly endemic for HBV infection and new strategies to promote HBV vaccination are to be adopted.

Intestinal parasites in healthy subjects in Albania.

The purpose of this study was to evaluate the prevalence of intestinal parasites in 277 healthy subjects in the city of Mamuras (Albania, South Eastern Europe) and the correlation between parasitic infections and possible risk factors. Faecal samples collected with sodium-acetate-formalin fixative were concentrated by formalin ethylacetate sedimentation and examined as wet mounts, permanent stains and by anti-Giardia/Cryptosporidium fluorescent antibodies. Data concerning age, sex, level of education, availability of piped water, number of people living in the same house, and residence in rural or urban area were collected for each subject. Statistical analysis was performed by chi-square test and regression logistic analysis. The overall prevalence of intestinal parasites was 183/277 (66.06%). In particular, pathogenic protozoa or helminths were found in 67 subjects (24.18%), including Trichuris trichiura in 34 (12.27%), Giardia duodenalis in 31 (11.19%), Hymenolepis nana in 5 (1.8%), Ascaris lumbricoides in 3 (1.08%). A significant correlation was observed only between parasite colonization and older age and between Trichuris trichiura infection and residence in rural areas.

Thalidomide plus monthly high-dose dexamethasone in chemorefractory myeloma. Results of a phase II clinical study.

Thalidomide is a potent anti-myeloma drug which can produce up to a 30-50% overall response rate (ORR) in pre-treated, chemorefractory multiple myeloma. Most authors agree with using 200 mg/daily with associated high dose dexamethasone (40 mg/daily x 4 days, 3 times monthly) considering lower doses investigational. We report our experience using thalidomide 100 mg/daily plus dexamethasone 40 mg/daily once a month, in 27 pre-treated patients. Thalidomide dose excalation and/or association with other drugs were established on the basis of the patient's response. Median age was 69 years (range 50-83 years) and 16 male and 11 female patients were treated. All patients had received more than 1 treatment line (range 1-5). Thalidomide was increased up to 300 mg/daily in 10 patients and 1 patient received up to 400 mg/daily. Two patients were not evaluable because of early death, 1 did not tolerate thalidomide because of pulmonary and neurological side-effects. Sixteen patients responded to this treatment, with an ORR of 66%. The combination of low-dose thalidomide plus monthly high-dose dexamethasone in chemorefractory myeloma showed interesting palliative results. According to our data, increasing thalidomide dosage and/or adding further drugs does not generally produce significant improvement.

Immunogenicity and Reactogenicity following Primary Immunisation with a Combined DTaP-HBV Vaccine and a Haemophilus influenzae Type B Vaccine Administered by Separate or Mixed Injection.

OBJECTIVES: The aim of this open, randomised, multicentre trial was to evaluate the immunogenicity and reactogenicity of the tetravalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTaP-HBV) vaccine when given either as a mixed or as a separate concomitant injection with the Haemophilus influenzae type b (Hib) vaccine at 3, 5 and 11 months of age. METHODS: Antibody against diphtheria, tetanus, pertussis (ELISA), hepatitis B (radioimmunoassay) and Hib polyribosylribitol phosphate (PRP) [radiolabeled antigen binding assay] was determined. Solicited local and systemic adverse events were evaluated on the day of each vaccination and for three subsequent days. Follow-up of unsolicited and serious adverse events was conducted for 30 days following each vaccination. RESULTS: A total of 360 subjects were enrolled in the study. After completion of the three-dose vaccination course, seroprotective antibody concentrations against diphtheria, tetanus and hepatitis B, together with a pertussis vaccine response, were seen in almost all subjects with immunogenicity results (n = 336). All subjects had post-vaccination Hib anti-PRP antibody concentrations of at least 0.15 mug/mL, and 97.0% and 99.4%, respectively, of the subjects receiving a single or separate injections had Hib anti-PRP antibody concentrations >/=1.0 mug/mL. Addition of the Hib vaccine to the tetravalent DTaP-HBV vaccine did not increase the incidence of local or systemic reactions. CONCLUSIONS: Combination of DTaP-HBV and Hib vaccines in a single injection is safe, immunogenic and well tolerated, and thus has the potential to simplify the childhood immunisation schedule in Italy.

Safety and immunogenicity profile of an experimental hepatitis B vaccine adjuvanted with AS04.

The reactogenicity and safety of an experimental hepatitis B (HB) vaccine containing adjuvant system (AS04) was compared with a licensed vaccine in a phase III, single-blind, randomised study in healthy volunteers >or=15 years of age. A total of 1303 subjects were enrolled to receive either two doses of HB-AS04 (0, 6 months) or three doses of the comparator vaccine (0, 1, 6 months). Two doses of HB-AS04 elicited seroprotection rates close to 100% and two-fold higher GMTs than the comparator vaccine. Results showed that both vaccines were well tolerated and the general safety profile of HB-AS04 was similar to that of the comparator vaccine.

Trisomy 8 in Philadelphia-negative cells during imatinib therapy.

Targeted therapy with imatinib selectively suppresses Philadelphia-positive cells in chronic myeloid leukemia cells, with reappearance of apparently normal hemopoiesis in a considerable number of patients. Recently, clonal abnormalities have been observed in Philadelphia-negative cells during imatinib therapy, the biologic and prognostic significance of which is actually unknown. A case of trisomy 8 occurring in Philadelphia-negative cells, which was treated by bone marrow transplantation, is reported. Chromosomal abnormalities in Philadelphia-negative cells do not seem to herald disease transformation, but the long-term prognosis may be influenced by an increased incidence of myelodysplasia in younger patients.

Intra-arterial hepatic chemoembolization in liver metastases from neuroendocrine tumors: a phase II study.

Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have a predisposition for metastasizing to the liver, causing parenchymal substitution and paraneoplastic syndrome. Lipiodol embolization combined with anticancer drugs is a recent tool in regional therapy. It has been proven that chemoembolization reduces tumor bulk and hormone levels, and that it palliates the symptoms of many patients with liver-dominant neuroendocrine metastases. Beginning in December 1988, ten patients with unresectable and chemotherapy-refractory liver metastatic neuroendocrine tumors were treated with chemoembolization based on a mixture of lipiodol, mitomycin, cisplatin, epirubicin, followed by gelfoam powder and contrast media. Toxicity encountered included: upper right quadrant pain requiring narcotics, elevation of lactate dehydrogenase, alkaline phosphatase, and transaminases. One patient had liver abscess and persistent fever for 2 weeks. We obtained two complete remissions lasting 12 and 34 months and 5 partial remissions. The median survival was 22 months. Four patients had urinary elevation of 5-hydroxyindolacetic acid (5-HIAA). They showed more than a 75% decrease in urinary secretion after treatment. In a patient with transplanted liver we noticed a partial response lasting 7 months. We conclude that chemoembolization will improve the clinical condition of a significant percentage of patients with liver metastases, that future therapy of carcinoid tumors will be based on specific tumor biology and that treatment will be customized for each individual patient combining the use of cytoreductive procedures including radiofrequency ablation, laser treatment and chemoembolization.

Hepatic intra-arterial chemotherapy (HIAC) of high dose mitomycin and epirubicin combined with caval chemofiltration versus prolonged low doses in liver metastases from colorectal cancer: a prospective randomized clinical study.

A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22).

Chemoresistant myeloma: phase II clinical study with low-dose thalidomide plus high-dose dexamethasone.

Thalidomide produces a response rate from 32 to 66% of pre-treated myeloma patients with doses ranging from 100 to 800 mg/daily. Common, dose-related side effects are sedation, constipation, polyneuropathy. Increased incidence of thromboembolic events were observed in myeloma patients receiving thalidomide as front-line therapy or in association with chemotherapy. Less common adverse reactions are central nervous system (CNS) dysfunction and cutaneous reactions. We describe the update of our experience with low dose thalidomide plus monthly high dose dexamethasone and zolendronate. Most patients were able to tolerate this regimen with few side effects. Erythrocyte sedimentation rate (ESR) lowering was early observed in patients who subsequently responded.

First-line intra-arterial chemotherapy (IAC) with epirubicin and mitoxantrone in locally advanced breast cancer.

BACKGROUND: Approximately 20% of patients with breast cancer present with locally advanced disease without distant metastases. This phase II double-center trial aimed at investigating the activity of epirubicin (Farmorubicin)--mitoxantrone (Onkotrone/Novantrone) combination as first-line intra-arterial chemotherapy (IAC) in locally advanced breast cancer patients. PATIENTS AND METHODS: Thirty-six patients with locally advanced disease and no prior exposure to anthracyclines received the following regimen: epirubicin (Farmorubicin) 30 mg/mq and mitoxantrone (Onkotrone/Novantrone) 10 mg/mq by IAC short infusion on day 1, every 3 weeks for up to six cycles. Prior to IAC an arteriogram of subclavian, internal mammary and lateral thoracic arteries was obtained in all patients, followed by infusion of a blue dye solution into the arteries to determine the most appropriate vessel that supplies the tumor area. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 25 patients (70%; 95%CI, 62% to 80%): 3 CR, 22 PR. Although three of the patients showed complete tumor regression, operative removal or toilet mastectomy became feasible in 25 patients since tumor shrinkage ranged over 75%. A total of 25 mastectomies were carried out for 36 patients. Four patients had bulky tumors (> 13 cm tumor diameter), while 8 patients had ulcerated tumors, two of which presented with complete infiltration of normal breast tissue. The median time to progression and median overall survival were 11 and 27 months, respectively. The time to local response was 3 weeks and time to mastectomy was 9 weeks. Transient neurological disorders developed in six patients and skin chemical burns with painful inflammatory reactions were encountered in ten patients. No systemic toxicity was observed in terms of bone marrow depression and hair loss. No cardiotoxicity was observed. In all specimens necrosis was reported (complete 3 cases, partial 16 and minimal 6). CONCLUSION: A combination of epirubicin (Farmorubicin) and mitoxantrone (Onkotrone/Novantrone) as IAC appears to be a safe and well tolerated treatment for locally advanced breast cancer without clinical evidence of distant metastases. When combined with surgery it offers interesting results in terms of local control and allows a high rate of mastectomies in otherwise inoperable cases.

Oxaliplatin plus raltitrexed in the treatment of patients with advanced colorectal cancer: a phase II study.

UNLABELLED: The combination of Oxaliplatin (OXA) and Raltitrexed (RTX) may represent a more convenient regimen as compared with OXA + 5-FU with Folinic acid (FA) modulation regimens. The present trial has been designed to explore the activity and tolerability of this combination in untreated and pretreated patients with advanced colorectal cancer (ACC). OXA and RTX were administered at the dose of 130 mg/m2 as i.v. 3-hour infusion and 3 mg/m2 over a 15-minute i.v. infusion, respectively, repeated every 21 days. Fifty patients were enrolled between February 1999 and March 2001. A total of 293 cycles were administered, with a median number of 6 cycles (range 1-14) per patient. The median dose intensity for OXA and RTX was 100% (50-100) and 86% (21-100), respectively. Reasons for RTX dose reduction were increases in transaminase serum levels and a reduction in creatinine clearance. Myelotoxicity was limited. A transaminase increase was observed in 74% of patients (14% grade 3 and 10% grade 4). Peripheral sensorial neurotoxicity was the most frequent side-effect (88%), although its intensity was mild in most patients (grade I 48%, grade II 24%, grade III 16%). Of 46 evaluable patients, 3 CR, 5 PR, 22 S and 16 P were observed. The CR + PR remission rate, according to the intention to treat analysis, was 16% with a 95% confidence limit of 7.2%-29.1%; in patients not pretreated for advanced disease the CR + PR rate was 26%, while only 2 out of 27 pretreated patients responded to the treatment (7%). The median time to progression was 5 months (2-11). The median survival was not reached after a median follow-up of 14 months. One-year survival is 60%. CONCLUSION: In this trial the OXA + RTX combination is confirmed to be active in ACC, although the level of activity seems to be lower than that of the other combination including OXA and 5-FU with or without FA modulation. The reasons for the low activity observed could at least in part be related to a reduction in the RTX dose intensity.

Tyrosine kinase inhibitor imatinib mesylate as anticancer agent for advanced ocular melanoma expressing immunoistochemical C-KIT (CD 117): preliminary results of a compassionate use clinical trial.

Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). It binds to the ATP-binding site of the target kinase and prevents the transfer of phosphate from ATP to the tyrosine residues of various substrates. At oral doses of 200-600 mg, the majority of patients with chronic myeloid leukaemia, Philadelphia chromosome-positive acute lymphoblastic leukemia expressing the BCR-ABL fusion protein and gastrointestinal stromal tumours (GIST) achieve a bio-molecular and clinical response, frequently complete, associated with limited toxicity. Several other human cancers, as small-cell lung carcinoma, melanoma, seminoma, some sarcomas, and adenoid cystic carcinomas may over-express KIT or PDGF-R, and clinical trials to evaluate the role of IM in the treatment of such cancers are currently ongoing. We determined c-KIT with Dako CD 117 antibody in 5 cases of advanced ocular melanoma (OM) and we found positive immuno-reactivity for CD 117 in three patients. We treated all patients with palliative-use IM at the oral dose of 400 mgr daily. We obtained in expressing positive immuno-reactivity for CD 117 patients: a reduction of malignant ascites in one, a partial remission in the neck nodes in another, and progression of liver metastases in the third. Evidences of progression has been reported in the other two patients expressing negative immuno-reactivity for CD 117. We conclude that the effect of IM should be assessed only in OM with positive immuno-histochemical c-kit (CD 117) expression. IM might be a potential therapeutic strategy for these patients.

Treatment of pseudomyxoma peritonei with two times--cytoreduction and hypertermic antiblastic peritoneal perfusion (HAPP).

Pseudomyxoma peritonei is a rare neoplasia with a low grade of clinical malignity in which neoplastic masses product large amount of mucinous material. Its treatment advocates an aggressive cytoreduction of all visceral and peritoneal lesions and Hyperthermic Antiblastic Peritoneal Perfusion (HAPP). In three cases we programmed a two stage surgical approach for the massive amount of peritoneal implants. Two times we achieved our aim, while one time, the wide progression of the disease during the two surgical procedures made useless our efforts to have a complete cytoreduction and the following HAPP. This last patient refused systemic chemotherapy between the two surgeries and we think that this should be one of the reasons of the failure.

Low-dose thalidomide plus monthly high-dose oral dexamethasone (Thali-Dexa): results, prognostic factors and side effects in eight patients previously treated with multiple myeloma.

Thalidomide is active both as single agent and in combination-therapy against refractory or relapsing multiple myeloma. Eigth patients previously treated were given Thalidomide 100mg/daily plus Dexametasone 40mg/daily for four days each month (Thali-Dexa) and followed for response, prognostic factors and side effects. Two patients had early death (one from massive cerebral ischemic stroke, the other from dementia and progressive renal failure), one patient progressed during Thali-Dexa (thalidomide 200mg) and was rescued with chemotherapy, two patients required increasing thalidomide dosage (to 200 and 400mg, respectively) because of progressive disease, three patients had stable disease remission lasting from 4m+ to 16m+. Thali-Dexa is a useful agent but age and vascular/metabolic diseases may increase the risk of severe side effects. Early decrease in erythrocyte sedimentation rate seems to correlate with better disease control.

Thyroid metastases from colon cancer case report in a long term survivor.

Colon cancer usually has an hematogenous spread to liver and lung: rarely, or in the case of most advanced disease, also brain and bone can be involved. Thyroid metastasis is generally thought to be infrequent, breast and kidney cancer being the most frequent causes. Herein we present the case of a man affected by liver metastasis from colon cancer, who developed unusual metastasis to thyroid.