Clinical classification of Swedish snuff dippers'' lesions supported by histology

From a total material of 184 Swedish users of loose packed moist snuff and 68 users of portion-bag packed moist snuff, cases were selected from subgroups based on a four-point clinical grading scale. The selected material for the study comprised 70 cases (ten from each clinical grade group, no Degree 4 lesion was found among portion-bag users). Features recognized in biopsies from these cases together with findings in previous studies correlated well with the use of a four-point scale for the grading of clinical changes, especially in the context of discriminating lesions for which special efforts should be undertaken to make the patient stop or change the snuff dipping habit and for selecting patients in whom regular clinical follow-up including a biopsy should be carried out. In this article is also discussed the labeling of the clinical oral mucosal changes seen at the site where a quid of snuff is regularly placed. The conceptual use of "snuff dippers' lesions" is recommended instead of e.g. snuff-induced leukoplakia.     

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy.

PURPOSE: For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS: In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.     

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA.

PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.     

A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma.

PURPOSE: Localized pancreatic carcinoma is rarely resectable and is resistant to conventional therapies. ONYX-015 (dl1520) is an E1B-55kD gene-deleted replication-selective adenovirus that preferentially replicates in and kills malignant cells. Endoscopic ultrasound (EUS) has the potential to conveniently and accurately deliver local therapy to the pancreas. Therefore, we undertook a trial of the feasibility, tolerability, and efficacy of EUS injection of ONYX-015 into unresectable pancreatic carcinomas. EXPERIMENTAL DESIGN: Twenty-one patients with locally advanced adenocarcinoma of the pancreas or with metastatic disease, but minimal or absent liver metastases, underwent eight sessions of ONYX-015 delivered by EUS injection into the primary pancreatic tumor over 8 weeks. The final four treatments were given in combination with gemcitabine (i.v., 1,000 mg/m(2)). Patients received 2 x 10(10) (n = 3) or 2 x 10(11) (n = 18) virus particles/treatment. RESULTS: After combination therapy, 2 patients had partial regressions of the injected tumor, 2 had minor responses, 6 had stable disease, and 11 had progressive disease or had to go off study because of treatment toxicity. No clinical pancreatitis occurred despite mild, transient elevations in lipase in a minority of patients. Two patients had sepsis before the institution of prophylactic oral antibiotics. Two patients had duodenal perforations from the rigid endoscope tip. No perforations occurred after the protocol was changed to transgastic injections only. CONCLUSIONS: This study indicates that ONYX-015 injection via EUS into pancreatic carcinomas by the transgastic route with prophylactic antibiotics is feasible and generally well tolerated either alone or in combination with gemcitabine. Transgastric EUS-guided injection is a new and practical method of delivering biological agents to pancreatic tumors.     

Risk management and system failure analysis in mental health investigations

This editorial explores the way in which mental health investigations are developing in England and in particular those involving a homicide. A move away from traditional panel inquiries and towards investigations using root cause analysis (RCA) is aimed at shifting the focus from individual blame to identifying system failure. Thus it is envisaged by policy makers that the RCA approach will offer greater learning opportunities for mental health services. The key difficulties associated with panel inquiries are highlighted before describing the intended benefits of the RCA approach. Finally, five key areas where systematic research can support the development of this approach are suggested.     

Overweight and obesity-related metabolic disorders in hospital employees.

BACKGROUND: Obesity is associated with metabolic disorders and cardiovascular diseases. This study investigated the relationship between overweight and obese status and the incidence of type 2 diabetes, hypertension, hyperlipidemia and hyperuricemia. METHODS: This prospective cohort study comprised 1749 hospital employees who received baseline health check-ups in 1993. Data from the 1027 participants (832 women, 195 men; mean age, 36 +/- 7 years) who repeated check-ups in 2003 were used in the analysis. Relative risks (RRs) for development of metabolic disorders during follow-up associated with different body mass index (BMI) categories at baseline as defined by Asia-Pacific recommendations and the Department of Health in Taiwan were calculated after adjustment for covariates. RESULTS: The prevalence of overweight and obesity at baseline check-up were 17.6% and 14.5%, respectively. Obese subjects with baseline BMI >or= 25 kg/m2 had a significant multivariate-adjusted RR of 2.7 for hypertension, 14.8 for type 2 diabetes, 3.2 for hypertriglyceridemia, and 2.8 for hyperuricemia, compared to subjects with baseline BMI < 23.0 kg/m2. RR for diabetes was higher in women than in men, but RR for hypertriglyceridemia was higher in men. The risks of hypertension and hyperuricemia significantly increased for subjects with baseline BMI >or= 23 kg/m2, while RRs for type 2 diabetes increased significantly for baseline BMI >or= 24 kg/m2 and hypertriglyceridemia increased for baseline BMI >or= 25 kg/m2. The risks attributable to obesity (baseline BMI >or= 25 kg/m2) were 23.0% for hypertension, 70.8% for diabetes, 27.9% for hypertriglyceridemia, and 24.1% for hyperuricemia. CONCLUSION: This study revealed that a high prevalence of overweight and obesity was associated with significantly increased risk of development of type 2 diabetes, hypertension, hypertriglyceridemia and hyperuricemia in hospital employees, suggesting the need for programs to improve weight management.     

Pain flare following external beam radiotherapy and meaningful change in pain scores in the treatment of bone metastases.

BACKGROUND AND PURPOSE: To examine the incidence of pain flare following external beam radiotherapy and to determine what constitutes a meaningful change in pain scores in the treatment of bone metastases. PATIENTS AND METHODS: Patients with bone metastases treated with external beam radiotherapy were asked to score their pain on a scale of 0-10 before the treatment (baseline), daily during the treatment and for 10 days after completion of external beam radiation. Pain flare was defined as a two-point increase from baseline pain in the pain scale of 0-10 with no decrease in analgesic intake or a 25% increase in analgesic intake employing daily oral morphine equivalent with no decrease in pain score. To distinguish pain flare from progression of pain, we required the pain score and analgesic intake to return back to baseline levels after the increase/flare. They were also asked to indicate if their pain changed during that time compared to pre-treatment level. The change in pain score was compared with patient perception. RESULTS: Eighty-eight patients were evaluated in this study. There were 49 male and 39 female patients with the median age of 70 years. Twelve of 88 patients (14%) had pain flare on day 1. The overall incidence of pain flare during the study period ranged from 2 to 16%. A total of 797 pain scorings were obtained. Patients perceived an improvement in pain when their self-reported pain score decreased by at least two points. CONCLUSIONS: Our study confirms the occurrence of pain flare following the external beam radiotherapy in the treatment of bone metastases. Further studies are required to predict who are at risk for flare. Appropriate measures can be taken to alleviate the pain flare. The finding in the meaningful change in pain scores supports the investigator-defined partial response used in some clinical trials.