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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Aberrantly activated AREG-EGFR signaling is required for the growth and survival of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells.

Salivary gland tumors (SGT) are a group of highly heterogeneous head and neck malignancies with widely varied clinical outcomes and no standard effective treatments. The CRTC1-MAML2 fusion oncogene, encoded by a recurring chromosomal translocation t(11;19)(q14-21;p12-13), is a frequent genetic alteration found in >50% of mucoepidermoid carcinomas (MEC), the most common malignant SGT. In this study, we aimed to define the role of the CRTC1-MAML2 oncogene in the maintenance of MEC tumor growth and to investigate critical downstream target genes and pathways for therapeutic targeting of MEC. By performing gene expression analyses and functional studies via RNA interference and pharmacological modulation, we determined the importance of the CRTC1-MAML2 fusion gene and its downstream AREG-EGFR signaling in human MEC cancer cell growth and survival in vitro and in vivo using human MEC xenograft models. We found that CRTC1-MAML2 fusion oncogene was required for the growth and survival of fusion-positive human MEC cancer cells in vitro and in vivo. The CRTC1-MAML2 oncoprotein induced the upregulation of the epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) by co-activating the transcription factor CREB, and AREG subsequently activated EGFR signaling in an autocrine manner that promoted MEC cell growth and survival. Importantly, CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR signaling inhibition. Therefore, our study revealed that aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival, suggesting that EGFR-targeted therapies will benefit patients with advanced, unresectable CRTC1-MAML2-positive MEC.

Diversity selection of compounds based on 'protein affinity fingerprints' improves sampling of bioactive chemical space.

Diversity selection is a frequently applied strategy for assembling high-throughput screening libraries, making the assumption that a diverse compound set increases chances of finding bioactive molecules. Based on previous work on experimental 'affinity fingerprints', in this study, a novel diversity selection method is benchmarked that utilizes predicted bioactivity profiles as descriptors. Compounds were selected based on their predicted activity against half of the targets (training set), and diversity was assessed based on coverage of the remaining (test set) targets. Simultaneously, fingerprint-based diversity selection was performed. An original version of the method exhibited on average 5% and an improved version on average 10% increase in target space coverage compared with the fingerprint-based methods. As a typical case, bioactivity-based selection of 231 compounds (2%) from a particular data set ('Cutoff-40') resulted in 47.0% and 50.1% coverage, while fingerprint-based selection only achieved 38.4% target coverage for the same subset size. In conclusion, the novel bioactivity-based selection method outperformed the fingerprint-based method in sampling bioactive chemical space on the data sets considered. The structures retrieved were structurally more acceptable to medicinal chemists while at the same time being more lipophilic, hence bioactivity-based diversity selection of compounds would best be combined with physicochemical property filters in practice.

High-calcium, vitamin D fortified milk is effective in improving bone turnover markers and vitamin D status in healthy postmenopausal Chinese women.

BACKGROUND/OBJECTIVES: Risk for developing osteoporosis increases in Asia. The purpose of the study was to evaluate the impact of a high-calcium vitamin D fortified milk (HCM) intervention on parathyroid hormone (PTH) levels, vitamin D status and markers of bone turnover in postmenopausal Chinese women. SUBJECTS/METHODS: Sixty three women (>55 years) were assigned to receive two servings of either a calcium/vitamin D fortified milk or a control drink for 12 weeks. PTH, serum 25 (OH)D levels, C-telopeptide of type I collagen (CTX) levels and procollagen type I N-terminal propeptide (PINP) were measured at baseline, 2, 8 and 12 weeks of supplementation. RESULTS: Daily calcium intake at baseline ranged between 260 and 482 mg for the HCM, and 252 and 692 mg for the control group. HCM improved serum 25 (OH)D levels significantly (33.13-39.49 nmol/l), while remaining similar in the control group (29.27-28.21 nmol/l). The difference between the groups were significant at week 2, 8 and 12. The percentage change in PTH levels in the HCM group was significant from week 2 onwards compared to the control drink (P<0.017, P<0.05 and P<0.001 at weeks 2, 8 and 12, respectively). Plasma CTX of the HCM group reduced by 25% between weeks 0 and 2, remaining significantly lower and at similar levels up to week 12. The difference between the HCM and control group for PINP reached significance at weeks 8 (P=0.011) and 12 (P=0.003). CONCLUSIONS: The HCM intervention significantly improved vitamin D status and reduced bone turnover over 12 weeks in postmenopausal Chinese women.

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.

Routine use of laparoscopic repair for perforated peptic ulcer.

BACKGROUND: Laparoscopic repair of perforated peptic ulcer was reported in 1990 but has not gained wide acceptance. The aim of this study was to evaluate the safety and efficacy of laparoscopic repair for perforated peptic ulcer in routine clinical practice. METHODS: This was a prospective analysis of 172 patients who underwent laparoscopic repair of a perforated peptic ulcer between July 1997 and June 2003. RESULTS: One hundred and seventy-two patients of mean age 54 (range 14-93) years had perforated peptic ulcer diagnosed by laparoscopy. There were 172 duodenal ulcers, 22 prepyloric and 13 non-juxtapyloric gastric ulcers. One hundred and sixty-five patients underwent omental patch closure of perforations; there were six Pólya gastrectomies and one ulcerectomy. Thirty-seven patients (21.5 per cent) required conversion to laparotomy. The mean operating time was 64.8 (range 14-180) min. The median postoperative requirement for intramuscular pethidine was one dose. The median postoperative hospital stay was 6 days. Complications occurred in 28 patients (16.3 per cent) resulting in three reoperations. Six patients with intra-abdominal collections were managed by percutaneous drainage. Two patients who underwent conversion developed a wound infection. Fourteen patients (8.1 per cent) died, 11 of whom were American Society of Anesthesiologists grade III and IV. CONCLUSION: Laparoscopic repair of perforated peptic ulcer is a safe emergency procedure in routine clinical practice for patients with perforated pyloroduodenal ulcer.

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.

Mutation analyses of 268 candidate genes in human tumor cell lines.

We have performed a homozygous deletion screen on 268 candidate genes in 90 human tumor cell lines derived from multiple types of cancers. Most of the candidate genes investigated have been proposed to be involved in cellular processes that are germane to cancer progression, such as cell cycle control, genome maintenance, chromatin remodeling, cell adhesion, and apoptosis. We have detected novel homozygous deletions affecting four independent loci: Brahma-related gene (SMARCA4) on chromosome 19p in the TSU-Pr1 prostate and A427 lung carcinoma lines, Map Kinase Kinase 3 (MAP2K3) on 17q in the NCI-H774 lung tumor cell line, TMPRSS2 on 21q in the Bx PC-3 pancreatic carcinoma line, and Cadherin 6 (CDH6) on 5p in the SK-LU-1 lung carcinoma line. Subsequent analyses of the coding sequences of these four genes using cDNAs from a panel of tumor cell lines revealed multiple sequence variants. The results of this mutation study serve to demonstrate the feasibility of performing high-throughput screens of candidate genes in tumor cell lines to identify genes that may be targeted for mutation during the development of cancer.

Anti-allergic activity of the Sophorae radix water extract in experimental animals.

The water extract of Sophorae radix was tested for its preventive effects against cardiovascular anaphylaxis elicited in experimental animals. In actively sensitized pithed rats, the extract partially protected the animals from death resulting from antigen challenge. Of the cardiovascular changes observed during the anaphylaxis in the pithed animals, the initial pressor response was significantly attenuated by the extract. The extract also improved anaphylactic cardiac dysfunction in passively sensitized isolated guinea hearts: improvement was noted in the contractility, arrhythmic duration and lactate dehydrogenase elevation. The perfusion pressure change to antigen challenge was not altered by the extract in passively sensitized isolated mesenteric artery preparations. The extract however significantly inhibited homologous passive cutaneous anaphylaxis responses in rats. When examined in isolated guinea pig tracheal muscle, the extract did not influence at reasonable concentrations on the contraction elicited by three major anaphylactic mediators, histamine, leukotriene D4 and serotonin. These results suggest that the water extract of Sophorae radix possesses anti-anaphylactic effect in cardiovascular system, primarily acting on the heart not the peripheral resistance vessels.