Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study.

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Population pharmacokinetics of ceftazidime in critically ill children: impact of cystic fibrosis.

BACKGROUND: Pharmacokinetics data on ceftazidime are sparse for the paediatric population, particularly for children with cystic fibrosis (CF) or severe infections. OBJECTIVES: To characterize the population pharmacokinetics of ceftazidime in critically ill children, identify covariates that affect drug disposition and evaluate the current dosing regimens. METHODS: The study was registered with Clinicaltrials.gov (NCT01344512). Children receiving ceftazidime were selected in 13 French hospitals. Plasma concentrations were determined by UPLC-MS/MS. Population pharmacokinetic analyses were performed using NONMEN software. RESULTS: One hundred and eight patients, aged 28 days to 12 years, with CF (n = 32), haematology and/or oncology disorders (n = 47) or severe infection (n = 29) were included. Ceftazidime was administered by continuous or intermittent infusions; 271 samples were available for analysis. A two-compartment model with first-order elimination and allometric scaling was developed and covariate analysis showed that ceftazidime pharmacokinetics were also significantly affected by CLCR and CF. Ceftazidime clearance was 82% higher in CF than in non-CF patients. Monte Carlo simulations showed that the percentage of target attainment (PTA) for the target of T>MIC = 65% was (i) lower in CF than in non-CF children with intermittent infusions and (ii) higher with continuous than intermittent infusion in all children. CONCLUSIONS: The population pharmacokinetics model for ceftazidime in children was influenced by body weight, CLCR and CF. A higher PTA was obtained with continuous versus intermittent infusions. Further studies should explore the benefits of continuous versus intermittent infusion of ceftazidime, including current versus increased doses in CF children.

Low incidence of BRCA2 mutations in breast carcinoma and other cancers.

Inherited mutant alleles of familial tumour suppressor genes predispose individuals to particular types of cancer. In addition to an involvement in inherited susceptibility to cancer, these tumour suppressor genes are targets for somatic mutations in sporadic cancers of the same type found in the familial forms. An exception is BRCA1, which contributes to a significant fraction of familial breast and ovarian cancer, but undergoes mutation at very low rates in sporadic breast and ovarian cancers. This finding suggests that other genes may be the principal targets for somatic mutation in breast carcinoma. A second, recently identified familial breast cancer gene, BRCA2 (refs 5-8), accounts for a proportion of breast cancer roughly equal to BRCA1. Like BRCA1, BRCA2 behaves as a dominantly inherited tumour suppressor gene. Individuals who inherit one mutant allele are at increased risk for breast cancer, and the tumours they develop lose the wild-type allele by heterozygous deletion. The BRCA2 coding sequence is huge, composed of 26 exons that span 10,443 bp. Here we investigate the rate of BRCA2 mutation in sporadic breast cancers and in a set of cell lines that represent twelve other tumour types. Surprisingly, mutations in BRCA2 are infrequent in cancers including breast carcinoma. However, a probable germline mutation in a pancreatic tumour cell line suggests a role for BRCA2 in susceptibility to pancreatic cancer.

Effects of plyometric- and cycle-based high-intensity interval training on body composition, aerobic capacity, and muscle function in young females: a field-based group fitness assessment.

High-intensity interval training (HIIT) is an effective alternative to moderate intensity continuous training for improvements in body composition and aerobic capacity; however, there is little work comparing different modalities of HIIT. The purpose of this study was to compare the effects of plyometric- (PLYO) and cycle-oriented (CYC) HIIT on body composition, aerobic capacity, and skeletal muscle size, quality, and function in recreationally trained females. Young (21.7 ± 3.1 yrs), recreationally active females were quasi-randomized (1:1 ratio) to 8 weeks of twice weekly PLYO (n = 15) or CYC (n = 15) HIIT. Body composition (four-compartment model), VO2peak, countermovement jump performance, muscle size, and echo intensity (muscle quality), as well as strength and power of the knee extensors and plantar flexors were measured before and after training. Both groups showed a similar decrease in body fat percentage (p < 0.001; η p 2   = 0.409) and echo intensity (p < 0.001; η p 2 = 0.558), and an increase in fat-free mass (p < 0.001; η p 2   = 0.367) and VO2peak (p = 0.001; η p 2 = 0.318). Muscle size was unaffected (p > 0.05), whereas peak torque was reduced similarly in both groups (p = 0.017; η p 2 = 0.188) and rapid torque capacity was diminished only for the knee extensors after CYC (p = 0.022; d = -0.67). These results suggest that PLYO and CYC HIIT are similarly effective for improving body composition, aerobic capacity, and muscle quality, whereas muscle function may express moderate decrements in recreationally active females. ClinicalTrials.gov (NCT05821504).

Energy crop as an environmentally sustainable reclamation option for post-mining sites: a life cycle assessment of cassava planting in Vietnam.

Using post-mining areas for planting energy crops has emerged as a promising and sustainable reclamation solution due to its potential contributions to environmental protection, land restoration, and especially energy security. However, to ensure the sustainability of this reclamation solution, its environmental performance needs to be thoroughly assessed case by case. Located in Ha Thuong Commune, Dai Tu District, Thai Nguyen Province in northern Vietnam, Nui Phao is the world's largest tungsten mine. To restore post-mining sites at Nui Phao, cassava planting for ethanol production was one of the proposed measures. To support the decision-making, this study employs life cycle assessment to thoroughly evaluate the environmental performance and potential environmental benefits/costs of cassava-based reclamation system in terms of resource consumption and green house gas (GHG) emission. The results show that cassava-based reclamation might bring significant environmental benefits in terms of fossil fuel saving and GHGs reduction (i.e., reduce 50% fossil fuel consumption and 36% GHGs emission); however, it does not bring any benefit in terms of water and land resource consumption. Moreover, the results define cassava cultivation as the "hot spot" of the system, where innovations to enhance the yield and reduce water and fertilizer consumption are required to improve the environmental performance of the cassava-based reclamation system.

Identifying SARS-CoV2 transmission cluster category: An analysis of country government database.

BACKGROUND: As a result of the high contagiousness and transmissibility of SARS-CoV-2, studying the location of the case clusters that will follow, will help understand the risk factors related to the disease transmission. In this study, we aim to identify the transmission cluster category and settings that can guide decision-makers which areas to be opened again. METHODS: A thorough review of the literature and the media articles were performed. After data verification, we included cluster data from eight countries as of 16th May 2020. Clusters were further categorized into 10 categories and analysis was performed. The data was organized and presented in an easily accessible online sheet. RESULTS: Among the eight included countries, we have found 3905 clusters and a total number of 1,907,944 patients. Indoor settings (mass accommodation and residential facilities) comprised the highest number of both number of clusters (3315/3905) and infected patients (1,837,019/1,907,944), while the outdoor ones comprised 590 clusters and 70,925 patients. Mass accommodation was associated with the highest number of cases in 5 of the 7 countries with data available. Social events and residential settings were responsible for the highest number of cases in the two remaining countries. In the USA, workplace facilities have reported 165 clusters of infection including 122 food production facilities. CONCLUSIONS: Lockdown could truly be a huge burden on a country's economy. However, with the proper knowledge concerning the transmissibility and the behaviour of the disease, better decisions could be made to guide the appropriate removal of lockdown across the different fields and regions.

Impact of National Economy and Policies on End-Stage Kidney Care in South Asia and Southeast Asia.

BACKGROUND: The association between economic status and kidney disease is incompletely explored even in countries with higher economy (HE); the situation is complex in lower economies (LE) of South Asia and Southeast Asia (SA and SEA). METHODS: Fifteen countries of SA and SEA categorized as HE and LE, represented by the representatives of the national nephrology societies, participated in this questionnaire and interview-based assessment of the impact of economic status on renal care. RESULTS: Average incidence and prevalence of end-stage kidney disease (ESKD) per million population (pmp) are 1.8 times and 3.3 times higher in HE. Hemodialysis is the main renal replacement therapy (RRT) (HE-68%, LE-63%). Funding of dialysis in HE is mainly by state (65%) or insurance bodies (30%); out of pocket expenses (OOPE) are high in LE (41%). Highest cost for hemodialysis is in Brunei and Singapore, and lowest in Myanmar and Nepal. Median number of dialysis machines/1000 ESKD population is 110 in HE and 53 in LE. Average number of machines/dialysis units in HE is 2.7 times higher than LE. The HE countries have 9 times more dialysis centers pmp (median HE-17, LE-02) and 16 times more nephrologist density (median HE-14.8 ppm, LE-0.94 ppm). Dialysis sessions >2/week is frequently followed in HE (84%) and <2/week in LE (64%). "On-demand" hemodialysis (<2 sessions/week) is prevalent in LE. Hemodialysis dropout rates at one year are lower in HE (12.3%; LE 53.4%), death being the major cause (HE-93.6%; LE-43.8%); renal transplants constitute 4% (Brunei) to 39% (Hong Kong) of the RRT in HE. ESKD burden is expected to increase >10% in all the HE countries except Taiwan, 10%-20% in the majority of LE countries. CONCLUSION: Economic disparity in SA and SEA is reflected by poor dialysis infrastructure and penetration, inadequate manpower, higher OOPE, higher dialysis dropout rates, and lesser renal transplantations in LE countries. Utility of RRT can be improved by state funding and better insurance coverage.

Submandibular Gland Transfer: A Potential Imaging Pitfall.

BACKGROUND AND PURPOSE: The Seikaly and Jha submandibular gland transfer surgery is performed to facilitate gland shielding during radiation therapy for head and neck tumors to circumvent radiation-induced xerostomia. It results in an asymmetric postsurgical appearance of the submandibular and submental spaces. Our purpose was to characterize the morphologic and enhancement characteristics of the transferred submandibular gland and identify potential pitfalls in postoperative radiologic interpretation. MATERIALS AND METHODS: This retrospective study identified patients with head and neck cancer who had undergone the submandibular gland transfer procedure at our institution. Chart reviews were performed to identify relevant oncologic histories and therapies. CT and MR neck imaging was reviewed to characterize morphologic and enhancement characteristics of the pre- and postoperative submandibular glands, as well as interpretive accuracy. RESULTS: Eleven patients with oropharyngeal and nasopharyngeal squamous cell carcinomas who underwent submandibular gland transfer were identified. The transferred glands were significantly lengthened in the anteroposterior dimension compared with contralateral glands (P < .001) and displaced anteriorly and inferiorly within the submandibular and submental spaces. Enhancement patterns of the transferred submandibular glands varied, depending on the time of imaging relative to the operation and radiation therapy. Submandibular gland transfer was acknowledged in the postoperative report in 7/11 cases. Errors in interpretation were present in 2/11 reports. CONCLUSIONS: After the submandibular gland transfer procedure, the submandibular and submental spaces lose their symmetric appearances as the transferred submandibular glands become lengthened and located more anteriorly and inferiorly, with variable enhancement characteristics. Familiarity with the postsurgical appearance of the transferred submandibular glands is key to accurate imaging interpretation.

Parent satisfaction with primary repair of paediatric cleft lip in Southwest China.

The purpose of this study was to investigate the key factors in relation to parent satisfaction with the primary repair of paediatric cleft lip. One hundred and ninety-five children born with cleft lip and/or palate aged between 3 months and 1 year were recruited, along with their caregivers. All patients underwent primary cleft lip repair, and a telephone interview was held with their main caregivers at 3 months postoperative. The level of satisfaction with each item included in a simplified Cleft Evaluation Profile was ascertained and recorded. Patient clinical data were obtained from the medical records. One hundred and thirty-eight (71%) parents reported satisfaction with the general outcome of surgery. Parents were satisfied with the appearance of the lip and profile of the face, but were dissatisfied with the appearance of the nose and teeth. Mothers of patients showed lower satisfaction levels than fathers and grandparents. Parental satisfaction with the appearance of the lip was lower for patients without a cleft palate than for those with a cleft palate. The results of this study suggest that most Chinese parents of children who undergo primary cleft lip repair express satisfaction with the surgical outcomes. Satisfaction with the appearance of the nose and teeth is low and this needs to be improved. Other factors are likely to influence expressions of satisfaction.

Human papillomavirus tumour status is not associated with a positive depression screen for patients with oropharyngeal cancer.

BACKGROUND: Several risk factors for depression in patients with oropharyngeal cancer have been determined. However, it is unknown whether human papillomavirus associated oropharyngeal cancer, which has a distinct clinico-demographic profile, modulates this risk. METHODS: A retrospective analysis was conducted of patients with oropharyngeal cancer. These patients had completed a 10-item depression screening questionnaire before receiving treatment for their disease from 2011 to 2014. Associations between patient or disease characteristics and depression screening questionnaire results were investigated. RESULTS: The study comprised 69 patients, 31 (44.9 per cent) of whom screened positive for depression. There were no significant differences in distributions of clinico-demographic or histopathological characteristics, including human papillomavirus tumour status, by depression screen result. CONCLUSION: This population has a high risk for depression, but no obvious risk factors, including human papillomavirus tumour status, were associated with an elevated risk. This inability to risk-stratify patients by clinico-demographic or disease characteristics emphasises the importance of regular depression screening for all patients in this population.

BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines.

Human BRG1 is a component of the evolutionarily conserved SWI-SNF chromatin remodeling complex. BRG1 has been implicated in growth control through its interaction with the tumor suppressor pRb and may consequently serve as a negative regulator of proliferation. Postulating that BRG1 may itself be a tumor suppressor gene, we screened a panel of tumor cell lines to determine whether the gene is targeted for mutation. We report that the COOH-terminal region of BRG1 is homozygously deleted in two carcinoma cell lines, prostate TSU-Pr1 and lung A-427. In addition, biallelic inactivations of BRG1 were observed in four other cell lines derived from carcinomas of the breast, lung, pancreas, and prostate; their mutations in BRG1 included three frameshift lesions and one nonsense lesion. Point mutations were also discovered in a number of other cell lines, however in most cases any effect of these mutations on BRG1 function remains to be established. A variety of different mutations within BRG1, in several cell lines, suggest that BRG1 may be targeted for disruption in human tumors. Significantly, reintroduction of BRG1 into cells lacking BRG1 expression was sufficient to reverse their transformed phenotype inducing growth arrest and a flattened morphology. These data strongly support the model that BRG1 may function as a tumor suppressor and strengthen the hypothesis that the regulation of gene expression through chromatin remodeling is critical for cancer progression. It will be important to confirm these observations in primary tumors.

Comparison of alternatives to passive surveillance to detect foot and mouth disease incursions in Victoria, Australia.

This study aimed to evaluate strategies to enhance the early detection of foot and mouth disease incursions in Australia. Two strategies were considered. First, improving the performance of the current passive surveillance system. Second, supplementing the current passive system with active surveillance strategies based on testing animals at saleyards or through bulk milk testing of dairy herds. Simulation modelling estimated the impact of producer education and awareness by either increasing the daily probability that a farmer will report the presence of diseased animals or by reducing the proportion of the herd showing clinical signs required to trigger a disease report. Both increasing the probability of reporting and reducing the proportion of animals showing clinical signs resulted in incremental decreases in the time to detection, the size and the duration of the outbreak. A gold standard system in which all producers reported the presence of disease once 10% of the herd showed clinical signs reduced the median time to detection of the outbreak from 20 to 15days, the duration of the subsequent outbreak from 53 to 42days and the number of infected farms from 46 to 32. Bulk milk testing reduced the median time to detection by two days and the number of infected farms by six but had no impact on the duration of the outbreak. Screening of animals at saleyards provided no improvement over the current passive surveillance system alone while having significant resource issues. It is concluded that the most effective way to achieve early detection of incursions of foot and mouth disease into Victoria, Australia is to invest in improving producer reporting.

Characterization of a carboxy-terminal BRCA1 interacting protein.

There are several lines of evidence indicating that the carboxy-terminal region of the tumor suppressor protein BRCA1 is a functionally significant domain. Using the yeast two-hybrid and in vitro biochemical assays, we show that a protein, CtIP, interacts specifically with the carboxy-terminal segment of human BRCA1 from residues 1602-1863. A germ line truncation mutation, Y1853ter, that removes the last 11 amino acids from the carboxy-terminus of BRCA1, abolishes not only its transcriptional activation function, but also binding to CtIP. The function of CtIP is unknown, but its reported association with a transcriptional repressor CtBP lends further support that it may have a role in transcription. A sequence based screen of a panel of 89 tumor cell line cDNAs for mutations in the CtIP coding region identified five missense variants. In the pancreatic carcinoma cell line, BxPC3, the non-conservative lysine to glutamic acid change at codon 337 is accompanied with apparent loss of heterozygosity or non-expression of the wild type allele. Thus it is plausible that CtIP may itself be a tumor suppressor acting in the same pathway as BRCA1.

Obesity is associated with increased risk of allergy in Vietnamese adolescents.

BACKGROUND: The prevalence of allergic diseases has remarkably increased in the last decades in tandem with the number of obese individuals. Results of studies on obesity and allergic diseases are controversial, and most of them are related to asthma and asthma-like symptoms. OBJECTIVE: In our study, we evaluated the association of several obesity indices and the prevalence of allergic diseases, including bronchial asthma, allergic rhino-conjunctivitis, atopic dermatitis and food allergy. DESIGN: Cross-sectional study. RESULTS: From a total of 1185 adolescents (49.3% boys) aged 12 to 17 y old, 19.3% reported a physician-diagnosed allergic disease, and 35.3% reported undiagnosed allergic symptoms. Logistic regression analysis revealed a higher risk of allergy in children of middle (OR = 2.02, CI: 1.12-3.64) and high (OR = 2.40, CI: 1.25-4.61) compared to low socioeconomic status, in subjects reporting industrial emissions in the neighborhood (OR = 2.19, CI: 1.40-3.41), and in adolescents with parental history of allergy (OR = 1.92, CI: 1.26-2.92). Body mass index (BMI) and percentage of body fat (%BF) were significantly related to allergy (OR = 1.16, CI: 1.01-1.34 for BMI; OR = 1.03, CI: 1.01-1.06 for %BF). After controlling for socioeconomic status, industrial emissions and parental history of allergy, only %BF remained statistically significant (OR = 1.03, CI: 1.01-1.06). Food allergy was not related to obesity in our study population, and when adolescents with food allergy were excluded from the analysis, the odds of having allergy increased 28% with each increase in SD of BMI (OR = 1.28, CI: 1.05-1.57) and 5% for each unit increase in the percentage of body fat (OR = 1.05, CI: 1.01-1.08). CONCLUSION: In conclusion, being overweight was associated with an increased risk of allergy in our study population. Our results point towards an association between being overweight and rhino-conjunctivitis, but not food allergy. No association was observed with other allergic diseases.

Results of treatment for chronic pancreatitis by the combined Frey and Beger procedure.

INTRODUCTION: The goal of this study was to evaluate the immediate and long-term outcomes after the combined Frey and Beger procedure for chronic pancreatitis. MATERIAL AND METHODS: From March 2008 to July 2011, 50 consecutive patients with chronic pancreatitis, confirmed by pathology, underwent the combined Frey and Beger procedure in the gastrointestinal surgery unit of Viet Duc hospital (Hanoi, Vietnam). RESULTS: The mean duration of operation was 280 ± 48.3min. The mean duration of postoperative hospital stay was 8.4 ± 1.8 days. Morbidity was 6%, and there was no postoperative mortality. After a mean follow-up of 24.8 months, pain subsided in 97.8% of patients, regain of weight was observed in 68.1% of patients (mean 3.7 kg), and 78.2% of patients were able to go back to normal activities. Endocrine and exocrine function was preserved in 83.0% and 91.5% of patients, respectively. CONCLUSIONS: The combined Frey and Beger procedure provides good antalgic control while preserving pancreatic function, with acceptable morbidity and mortality.

Effect of dietary selenium restriction on selected parameters of selenium status in men with high life-long intake.

The influence of selenium (Se) restriction on disposition in plasma and urine fractions of infused (74)Se (selenite) was studied when adult males (Enshi City, Hubei Province, PRC) whose habitual daily Se intake is approximately 480 microg per day were transferred to Lichuan County, where the daily intake is approximately 30 microg. The subjects received an infusion (106 microg Se) on the day before consuming foods low in Se and a second infusion (113 microg Se) 63 days later. Blood and 24-hour urine samples were collected each day for 7 days after the first infusion and on days 22, 43, and 62 following the first infusion. Urine and blood were also collected daily for the next 7 days after the second infusion. Plasma total Se concentration increased for 7 days after each of the two infusions and urine Se decreased exponentially following both the first and second infusions. The excretion of trimethylselenonium followed the same pattern as the total urinary Se. Surprisingly, there was not a significant difference in selenite retention between the two infusion periods, and the data indicated that, regardless of the chemical form of Se present in various organs, its catabolism leading to excretion in urine followed the same pathway as that of selenite. Labeled Se was incorporated predominantly in the plasma selenoprotein P fraction and the half-life of Se in this fraction was determined to be 1.9 to 2.9 days. Thus, a longer depletion period is required in these subjects to obtain more significant changes.

Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology-proven hepatocellular carcinoma.

INTRODUCTION: Serum alpha-fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), although the serum AFP concentration is also increased in patients with chronic liver diseases (CLD). The analysis of AFP glycoforms has been known to be of diagnostic value. We applied the lectin-affinity electrophoresis and antibody-affinity blotting techniques to HCC patients in Vietnam in order to better understand the role of lentil lectin-affinity AFP-L3 in the diagnosis and differential diagnosis of HCC, and its relationship with the biological characteristics of HCC. METHODS: Lens culinaris agglutinin-reactive AFP (AFP-L3) was measured in 65 patients with histologically proven HCC and 25 patients with CLD. All patients had serum AFP levels above 54 ng/mL. AFP-L3 levels were determined by lectin affinity electrophoresis coupled with antibody-affinity blotting. The diagnosis of HCC was confirmed histologically by ultrasound-guided biopsy. RESULTS: The mean value of AFP-L3 in the HCC patients was 49.6 +/- 21.6%, which was significantly higher (p<0.001) than that in the 25 CLD patients (10.7 +/- 4.3%). When the cutoff level for AFP-L3 was set at 15% (mean +/- SD), the sensitivity was 96.9%, the specificity 92.0% and the accuracy 95.5% in the 65 HCC patients. There was no clear correlation between serum AFP level and AFP-L3 percentage (r=0.16). There was no correlation between AFP-L3 and the maximum diameter of HCC nodules (r=0.05). However, the mean AFP-L3 value was higher in moderately or poorly differentiated HCC than in well differentiated tumors (p<0.001). CONCLUSIONS: AFP-L3 is potentially a clinically useful marker for the differentiation of increased AFP levels in hepatocellular carcinoma and chronic liver diseases. The AFP-L3 percentage is closely related to HCC differentiation. We consider the analysis of AFP-L3 a useful adjunct in the diagnosis of HCC.

Osteosarcoma of the head and neck: a review of the Johns Hopkins experience.

OBJECTIVE: To determine factors including treatment modalities which influence survival in patients with osteosarcoma of the head and neck. STUDY DESIGN: Retrospective clinicopathologic study of 27 patients with osteosarcoma of the head and neck. METHODS: The clinical charts and pathology slides were reviewed on 27 patients who had osteosarcoma of the head and neck between 1946 and 1998. The following variables were examined for their effect on survival: age of diagnosis, site of tumor, presentation, race, sex, prior radiation exposure, retinoblastoma history, margin status, and method of treatment. RESULTS: The average age at the time of diagnosis of the patients was 37.6 years (range, 7-82 y). The sex distribution was similar with 14 male and 13 female patients. Eight of 27 patients had osteosarcoma of the mandible, 9 of 27 had osteosarcoma of the maxilla and paranasal sinuses, and in 10 of 27 patients osteosarcoma occurred elsewhere, including the temporal bones, occipital bones, and orbit. The overall 2-year survival was 66% with a 5-year survival rate of 55%. CONCLUSIONS: Positive surgical margins and a high tumor grade were found to have a statistically deleterious effect on overall survival. There was no detectable effect on survival of age, race, sex, prior radiation exposure, tumor site, and tumor cell type. It was not possible to differentiate between the different adjuvant treatment modalities because of the small numbers in the study.

Genetics of pancreatic cancer. From genes to families.

Cancer of the pancreas is a genetic disease. Sporadic cancers of the pancreas are frequently associated with the activation of an oncogene, K-ras, and the inactivation of multiple tumor suppressor genes, including p53, DPC4, p16, and BRCA2. An improved understanding of the genetics of pancreas cancer should lead to new tests to screen for this disease and novel rational gene-based therapies.