Cytochrome P450 2A6 polymorphism in nasopharyngeal carcinoma

Nitrosamine has been identified as a carcinogen for nasopharyngeal carcinoma (NPC). Here, we investigated if a nitrosamine metabolizing gene, cytochrome P450 2A6 (CYP2A6) played an important role in NPC development. Relationships between the disease and the CYP2A6 were studied in 74 NPC patients and 137 age-matched healthy controls by using PCR-RFLP assay to distinguish between a wide type allele, *1A, and two mutant alleles, *1B and *4C. Overall, a significant association between CYP2A6 polymorphism and NPC development was observed (P<0.05). Individual with mutant alleles had an increased risk for NPC when compared to those with *1A/*1A (OR=2.37, 95% CI=1.27–4.46). In addition, males who carried mutant alleles of CYP2A6 had a fivefold increased risk for NPC when compared with those who carried *1A/*1A genotype (OR=5.02, 95% CI=1.82–14.14). It is thus suggested that CYP2A6 polymorphism may play a crucial role in NPC susceptibility and it may be used as a risk marker for NPC.     

Cisplatin, gemcitabine, and ifosfamide as weekly therapy: a feasibility and phase II study of salvage treatment for advanced transitional-cell carcinoma.

PURPOSE: We investigated the feasibility, safety, and antitumor activity of weekly gemcitabine given in combination with low doses of cisplatin and ifosfamide in previously treated patients with advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, metastatic or unresectable TCC who had received one or two prior chemotherapy regimens were eligible. On a 28-day course, doses of cisplatin 30 mg/m(2), gemcitabine 800 mg/m(2), and ifosfamide 1 g/m(2) were given on day 1 and then repeated on day 8 and day 15 unless there was dose-limiting hematologic toxicity. RESULTS: Fifty-one patients were registered; 10 patients participated in a pilot study, after which 41 patients were registered onto the phase II protocol. Forty-eight patients (94.1%) had dose-limiting hematologic toxicity on day 8 or day 15. Nonhematologic toxicity of grade 3 or greater consisted mainly of nausea and vomiting (seven patients, 13.7%) and infection (seven patients, 13.7%). Responses could be assessed in 49 of 51 eligible patients; two complete responses (4.1%) and 18 partial responses (36.7%) were observed for an overall response rate of 40.8% (exact 95% confidence interval, 27% to 56%). CONCLUSION: This regimen of cisplatin, gemcitabine, and ifosfamide is not feasible for weekly administration because of hematologic toxicity. Nevertheless, there was promising activity with only two doses per 28-day cycle. On the basis of these results, we have initiated a phase II trial of this combination given as a single dose every 14 days in patients with untreated, metastatic urothelial carcinoma.     

SHORT COMMUNICATION: Promotion of cholangiocarcinogenesis in the hamster liver by bile duct ligation after dimethylnitrosamine initiation

Administration of hepatocardnogenic nitrosamines before or afterinfection with the liver fluke, Opisthorchis viverrini (OV),results in marked development of cholangiocellular and hepatocellularprecancerous and cancerous lesions in the hamster liver. Thepromoting effects of OV are believed to be exerted either mechanically,chemically or immuno-logically. To test the influence of possiblemechanical effects, Syrian hamsters were initiated with a singlei.p. injection of dimethylnitrosamine (DMN) 20 mg/kg and subjected2 weeks later either to a sham operation or to complete ligationof the extrahepatic bile duct to the left lateral lobe. At theend of week 40, the animals receiving DMN-initiation and ligationhad a 60.9% incidence of cholangiofibrosis, 21.7% of mucouscystadenomas and 39.1% of cholangiocarcinomas, whereas the groupgiven DMN alone only developed cholangiofibrosis, limited to5% of the animals. In the latter case neither cystadenomas norcholangiocarcinomas were observed. The incidence of hepatocellularnodules did not differ between the two groups and no tumorouslesions developed in either the ligated or the untreated groupswithout DMN pretreatment. Complete ligation of the bile ductitself led to a series of events; obstruction of bile flow beingfollowed by dilatation, cyst formation, and necrosis of thebile duct epithelium and surrounding affected areas leadingto regenerative proliferation. The results are in line withthe conclusion that parasite-associated proliferation in targetcell populations is, at least in part, responsible for the influenceof OV on liver tumor development.     

Outbreak of infections caused by Enterobacter cloacae producing the integron-associated beta-lactamase IBC-1 in a neonatal intensive care unit of a Greek hospital

Nineteen of 27 ceftazidime-resistant Enterobacter cloacae isolates from a neonatal intensive care unit in Thessaloniki, Greece, had genes coding for the novel extended-spectrum beta-lactamase IBC-1; 18 of those 19 harbored similar conjugative plasmids and belonged to two distinct genetic lineages. A synergy test with ceftazidime and imipenem enabled us to identify five unrelated bla(IBC-1)-carrying E. cloacae isolates from other wards of the hospital. It seems that this integron-associated gene is capable of dispersing both by clonal spread and by gene dissemination.     

Trichosporon asahii: an unusual cause of invasive infection in neonates

Trichosporon asahii causes white piedra, an infection of hair shafts and onychomycosis in immunocompetent patients, as well as various localized or disseminated invasive infections in immunodeficient hosts. We describe a 26-week gestation 890-g vaginally delivered female neonate who had severe respiratory distress syndrome and on the sixth day of life developed Klebsiella pneumoniae sepsis. At the same time two blood cultures were positive for T. asahii. The neonate was also colonized with T. asahii in the pharynx and perineum. The infant was successfully treated with conventional amphotericin B.     

Exocrine Pancreatic Function among Diabetic Patients in Thailand

Pancreozymin-secretin-stimulated secretion was measured for volume, bicarbonate concentration and total amylase output in 16 noninsulin-dependent patients and 23 age-, sex-, and weight-matched similar control subjects. Another group of 17 insulin-dependent patients was studied using secretin stimulation and the secretory response compared to a similar group of 37 control subjects. Pancreozymin-secretin-stimulated pancreatic function was normal in noninsulin-dependent patients. Abnormal values for at least one parameter of secretion were found in 82% of insulin-dependent patients. Amylase output was low in 35% and bicarbonate concentration was low in 30%. Hypersecretion occurred in 35%. One patient had abnormal values for all three parameters and three patients had two abnormal values. Hypersecretory response to secretin stimulation is considered to be an early finding of pancreatic exocrine dysfunction among insulin-dependent patients. Progressive secretory failure occurs as the pathological process increases, and a decrease in total amylase output becomes the most significant abnormality.     

Psychosocial functioning of young adolescent and adult survivors of childhood cancer

Goals of work The present study aimed to assess the psychosocial well-being of Greek adolescent and young adult survivors of childhood cancer and, in particular, self-esteem, anxiety, coping strategies, and social functioning. Patients and methods The sample comprised 103 Greek childhood cancer survivors and 135 healthy controls. The Battle Culture-free Self-esteem Inventory (BCSEI), the Spielberger State–Trait Anxiety Inventory (STAI), the Lazarus and Folkman Ways of Coping, and 36-item short-form instruments were used along with The Questionnaire for the Quality of Life. Main results Survivors scored higher than controls on all STAI subscales, but on State, the difference was statistically significant only for female adults, while on the Trait subscale, for the entire group. Survivors scored lower on Personal and higher on Lie subscale of BCSEI, by comparison to controls. When coping with stressful events, the use of self-blame strategies and wishful thinking were more frequent among controls, while distancing strategies more common among survivors. Conclusions The long-term psychological functioning of Greek survivors of childhood cancer is satisfactory, with emotional difficulties, such as increased anxiety and lower self-esteem, receding over time. Survivors experience personal growth and mature through trauma as they develop a positive view of the impact that the cancer experience has upon their life.