Induction of Dectin-1 and asthma-associated signal transduction pathways in RAW 264.7 cells by a triple-helical (1, 3)-ß-D glucan, curdlan.

People living in damp buildings are typically exposed to spore and mycelial fragments of the fungi that grow on damp building materials. There is experimental evidence that this exposure to triple-helical (1, 3)-ß-D glucan and low molecular weight toxins may be associated with non-atopic asthma observed in damp and moldy buildings. However, the mechanisms underlying this response are only partially resolved. Using the pure (1, 3)-ß-D glucan, curdlan, and the murine macrophage cell line, RAW 264.7, there were two objectives of this study. The first was to determine whether signal transduction pathways activating asthma-associated cell signaling pathways were stimulated using mouse transduction Pathway Finder(®) arrays and quantitative real-time (QRT) PCR. The second objective was to evaluate the dose and temporal responses associated with transcriptional changes in asthma-associated cytokines, the signal transduction receptor gene Dectin-1, and various transcription factor genes related to the induction of asthma using customized RT-PCR-based arrays. Compared to controls, the 10(-7) M curdlan treatment induced significant changes in gene transcription predominately in the NFkB, TGF-ß, p53, JAK/STAT, P13/AKT, phospholipase C, and stress signaling pathways. The 10(-8) M curdlan treatment mainly induced NFkB and TGF-ß pathways. Compared to controls, curdlan exposures also induced significant dose- and time-dependent changes in the gene translations. We found that that curdlan as a non-allergenic potentiator modulates a network of transduction signaling pathways not only associated with TH-1, TH-2, and TH-3 cell responses including asthma potentiation, but a variety of other cell responses in RAW 264.7 cells. These results help provide mechanistic basis for some of the phenotypic changes associated with asthma that have been observed in in vitro, in vivo, and human studies and open up a hypothesis-building process that could explain the rise of non-atopic asthma associated with fungi.

Unplanned excision of soft tissue sarcoma results in increased rates of local recurrence despite full further oncological treatment.

BACKGROUND: Unplanned excision of soft tissue sarcoma (STS) accounts for up to 40% of all initial operations for STS and is undertaken when the mass is presumed to be benign. The effect this has on outcome has never been fully established. METHODS: Patients with extremity or trunk STS between 2001 and 2005 who were treated by an initial inadvertent operation and then referred immediately to our unit were identified. Outcomes were compared with a control group of patients with STS who were stage-matched and had been treated conventionally by core biopsy and definitive surgery. Endpoints were local recurrence, distant metastases and sarcoma-specific survival. RESULTS: 134 patients who had undergone unplanned excision of STS were identified. One hundred twenty-one underwent further re-excision, and 51 (48%) of these patients had residual tumour identified after surgical re-excision. Two hundred nine stage-matched controls were identified who were treated conventionally. Median follow-up was 51.6 months. Local recurrence rates were considerably higher in the study group (23.8 vs. 11%, p = 0.0016), despite the control group having more stage 3 tumours. When the tumours were matched by stage, an increase in local recurrence was seen across all stages but was most pronounced for stage 3 tumours (37.5 vs. 14.2%, p = 0.005). Metastasis-free and sarcoma-specific survival were also significantly increased for stage 3 tumours. CONCLUSION: Unplanned initial excision of extremity soft tissue sarcoma may compromise long-term local control of extremity STS despite full further oncological management.

Inflammation-associated gene transcription and expression in mouse lungs induced by low molecular weight compounds from fungi from the built environment.

Few metabolites from fungi found indoors have been tested for inflammatory mediators endpoints in primary cultures of alveolar macrophages or in vivo. In this study, mice were intratracheally instilled with a single dose comprising 4x10(-5)moletoxin/kg lung wt dose of either atranone C, brevianamide, cladosporin, mycophenolic acid, neoechinulin A & B, sterigmatocystin or TMC-120A. These toxins are from fungi common on damp building materials. The dose used was comparable to the estimated doses of possible human exposure. Hematoxylin and eosin (H&E) histology and Alcian Blue/Periodic Acid Schiff (AB/PAS) histochemistry were used to evaluate lungs for time course (4h and 12h post-exposure (PE)) inflammatory and toxic changes. Reverse-transcription (RT)-PCR based arrays were also employed to evaluate time course inflammation-associated gene transcription in lung tissues of the different toxins. Immunohistochemistry (IHC) was used to probe MIP-2 and Tnf-alpha protein expression in treatment lungs to determine whether responses correspond with gene transcription data. Both histology and histochemistry revealed that toxin exposed lungs at 12h PE showed evidence of inflammation. H&E revealed that bronchioli were lined with irregularly thickened and sometimes sloughing epithelium and bronchiolar spaces supported infiltration of leukocytes, cellular and mucus-like debris while alveolar spaces supported swollen macrophages and modest amorphous debris accumulations. All toxin-instilled lungs exhibited copious mucus production and alveolar macrophages with red stained cytoplasm on bronchiolar surfaces, especially at 12h PE. Array analysis of 83 inflammation-associated genes extracted from lung tissue demonstrated a number of patterns, compared to controls. 82 genes assayed at 4h PE and 75 genes at 12h PE were significantly altered (p< or =0.05; >or =1.5-fold or < or =-1.5-fold change) in the different treatment animal groups. Expression of transcriptionally regulated genes was confirmed using immunohistochemistry that demonstrated MIP-2 and Tnf-alpha staining in respiratory bronchiolar epithelia, alveolar macrophages and alveolar type II cells. The transcriptional regulation in these genes in the treatment groups suggests that they may serve central roles in the immunomodulation of toxin-induced pro-inflammatory lung responses. Hierarchical cluster analysis revealed significant patterns of gene transcription linking the response of the toxins at equimolar doses in three groups: (1) brevianamide, mycophenolic acid and neoechinulin B, (2) neoechinulin A and sterigmatocystin, and (3) cladosporin, atranone C and TMC-120. The results further confirm the inflammatory nature of metabolites/toxins from such fungi can contribute to the development of non-allergenic respiratory health effects.

Inhibin betaB expression in murine adipose tissue and its regulation by leptin, insulin and dexamethasone.

Inhibin betaB (INHBB; coding for the activin betaB subunit) has previously been identified in both human and rodent adipose tissue and using Taqman real-time PCR with specific primers we confirm the expression of INHBB mRNA in rodent adipose tissue. Expression of INHBB in murine epididymal adipose tissue was higher than in any of the other tissues studied and appears to be regulated by changes in energy balance and leptin. It was increased fourfold in the epididymal fat depot of ob/ob mice compared with the same fat depot in lean mice. The i.p. administration of leptin in obese ob/ob mice decreases the expression of INHBB. In human adipose tissue, INHBB is reduced by weight loss. In keeping with this, we demonstrate that INHBB expression in murine adipose tissue is decreased in fasting and increased upon refeeding. We show that INHBB is expressed in both the mature adipocyte and the stromal vascular fraction of adipose tissue. INHBB increases with the differentiation of pre-adipocytes into mature adipocytes in the 3T3-L1 cell line. In differentiated 3T3-L1 adipocytes, where receptors to activin have been previously reported, insulin increases the expression of INHBB, while dexamethasone decreases the expression of INHBB when compared with untreated control cells. Taken together, these results suggest that the regulation of INHBB expression in adipose tissue may play a physiological role in energy balance or the insulin insensitivity associated with obesity.

Chlamydia trachomatis YtgA is an iron-binding periplasmic protein induced by iron restriction.

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium that is the causative agent of common sexually transmitted diseases and the leading cause of preventable blindness worldwide. It has been observed that YtgA (CT067) is very immunogenic in patients with chlamydial genital infections. Homology analyses suggested that YtgA is a soluble periplasmic protein and a component of an ATP-binding cassette (ABC) transport system for metals such as iron. Since little is known about iron transport in C. trachomatis, biochemical assays were used to determine the potential role of YtgA in iron acquisition. (59)Fe binding and competition studies revealed that YtgA preferentially binds iron over nickel, zinc or manganese. Western blot and densitometry techniques showed that YtgA concentrations specifically increased 3-5-fold in C. trachomatis, when cultured under iron-starvation conditions rather than under general stress conditions, such as exposure to penicillin. Finally, immuno-transmission electron microscopy provided evidence that YtgA is more concentrated in C. trachomatis during iron restriction, supporting a possible role for YtgA as a component of an ABC transporter.

Expression of neuromedin B in adipose tissue and its regulation by changes in energy balance.

Bombesin is one of the most powerful substances showing anorexic effects in the hypothalamus (Moody TW & Merali Z 2004 Bombesin-like peptides and associated receptors within the brain: distribution and behavioral implications. Peptides 25 511-520). In mammals, neuromedin B (NMB) is one member of a family of bombesin-like peptides, which have been shown to reduce food intake when administered systemically. Using Taqman real-time PCR with specific primers, we report the expression of NMB mRNA in both human and rodent adipose tissue. Expression of NMB in rodent epididymal adipose tissue was higher than in other tissues studied. Expression of NMB in adipose tissue appears to be regulated by changes in energy balance and leptin. It is decreased fourfold in the epididymal fat depot of ob/ob mice when compared with the same fat depot in lean mice. It is further decreased with the intra-peritoneally (i.p.) administration of leptin in both lean and obese ob/ob mice. This may relate to its function in food intake regulation or to changes in energy expenditure. We demonstrate that NMB expression in rodent adipose tissue is decreased in cold exposed animals. However, when we investigated the effects of NMB on resting metabolic rate by i.p. injection, there was no effect on oxygen consumption, RQ or physical activity when compared with saline-treated controls. In conclusion, NMB is expressed in both human and rodent adipose tissue and appears to be regulated by changes in energy balance. Given its anorexic effects centrally, it may form part of a new adipose tissue--hypothalamic axis regulating food intake.

Indoor air quality risk factors for severe lower respiratory tract infections in Inuit infants in Baffin Region, Nunavut: a pilot study.

Inuit infants have extremely high rates of lower respiratory tract infection (LRTI), but the causes for this are unclear. The aims of this study were to assess, in young Inuit children in Baffin Region, Nunavut, the feasibility of an epidemiologic study of the association between indoor air quality (IAQ) and respiratory health; to obtain data on IAQ in their housing; and to identify and classify risk factors for LRTI. Twenty houses in Cape Dorset, Nunavut with children below 2 years of age, were evaluated using a structured housing inspection and measurement of IAQ parameters, and a respiratory health questionnaire was administered. Twenty-five percent of the children had, at some time, been hospitalized for chest illness. Houses were very small, and had a median of six occupants per house. Forty-one percent of the houses had a calculated natural air change rate <0.35 air changes per hour. NO(2) concentrations were within the acceptable range. Smokers were present in at least 90% of the households, and nicotine concentrations exceeded 1.5 microg/m(3) in 25% of the dwellings. Particulates were found to be correlated closely with nicotine but not with NO(2) concentrations, suggesting that their main source was cigarette smoking rather than leakage from furnaces. Mattress fungal levels were markedly increased, although building fungal concentrations were low. Dust-mites were virtually non-existent. Potential risk factors related to IAQ for viral LRTI in Inuit infants were observed in this study, including reduced air exchange and environmental tobacco smoke exposure. Severe lower respiratory tract infection is common in Inuit infants. We found reduced air change rates and high occupancy levels in houses in Cape Dorset, which may increase the risk of respiratory infections. This suggests the measures to promote better ventilation or more housing may be beneficial. Further health benefits may be obtained by reducing bed sharing by infants and greater turnover of mattresses, which were found to have high levels of fungi.

Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects.

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response.

Concurrent HLA-related response factors mediate recombinant hepatitis B vaccine major adverse events.

Recombinant hepatitis B (HB) vaccines have successfully reduced infection, cirrhosis and carcinoma, but questions have endured about causality of serious adverse events following vaccination. After an event in a pediatric patient an investigation reviewed HLA vaccine response effects and analyzed genetics in reported cases. There are apparent common causal immune mechanisms among reported adverse events. HLA class II alleles/haplotypes linked to HB vaccine cellular/non-response and Crohn's disease can create conditions that actively/passively amplify, respectively, all or other components of the immune response to the HB vaccine. Presence of the HLA class I allele A2 can result in heavy cytotoxic T-cell activation and vaccine/self-peptide presentation to immune cells. If HLA autoimmune susceptibility alleles/haplotypes are present that control other immune response components, the probability is elevated that these will activate cross-reactive immune cells; the cells, their inflammatory secretions and/or auto-antibodies may initiate adverse events reflecting those susceptibilities. Probable DRB1 amplifying alleles are noted. High-resolution DNA typing and results analysis are described to test the hypothesis in known HB vaccine adverse event patients. Possible practical applications stemming from hypothesis validation are described.

Gas exchange during exercise in habitually active asthmatic subjects.

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency.

Laser therapy for an obstructing primary tracheal lymphoma in a patient with AIDS.

A patient with AIDS presented with progressive dyspnea leading to respiratory failure with near complete airway obstruction due to primary tracheal lymphoma. Laser therapy was used locally to debulk the tumour, which facilitated extubation and led to definitive treatment with chemotherapy. Alternatives for local airway control are discussed.

Development of a urinary biomarker of human exposure to deoxynivalenol.

Deoxynivalenol (DON) is a mycotoxin frequently found as a contaminant of cereal crops and may be etiologically associated with adverse health effects in developing countries where considerable quantities of contaminated crops are consumed. We investigated the metabolism of DON in rats as a basis to establish methodology for a candidate biomarker of human exposure to this toxin and tested this methodology on urine samples from a potentially highly exposed population. Sprague-Dawley rats received a single dose of [14C]DON (5.0+/-0.1 mg/kg body weight, 5.5+/-0.1 microCi/kg) and the distribution of DON in body fluids was investigated over 72 h. DON and its metabolites were detectable in the plasma of rats with the highest levels at 8 h, at which time approximately 9% was bound to plasma protein. A total of 37% of the administered DON was excreted in the urine and DON-glucuronide was implicated as the major urinary metabolite based on reverse-phase HPLC analysis of beta-glucuronidase- and sulphatase-treated samples. An immunoaffinity column (IAC)-HPLC method was subsequently developed to measure urinary metabolites, with a view to establishing a urine-based human biomarker. Urine samples were collected from female inhabitants of Linxian County, China, a high risk region for oesophageal cancer (OC) and an area of potentially high DON exposure, and Gejiu, a low risk region in China. DON was detected in all 15 samples following beta-glucuronidase treatment and IAC enrichment with the identity of DON being confirmed by mass spectrometry. The mean levels of DON from the suspected high and low exposure regions of China were 37 ng/ml (range 14-94 ng/ml) and 12 ng/ml (range 4-18 ng/ml), respectively. This is estimated to correspond to daily exposures of 1.1-7.4 microg/kg/day and 0.3-1.4 microg/kg/day, respectively. This is the first reported measurement of a urinary biomarker for DON in both animals and humans and should facilitate epidemiological studies of disease associations with this mycotoxin.

Effect of fibrin glue on air leak and length of hospital stay after pulmonary lobectomy.

AIM: Air leaks are a common cause of morbidity and prolonged hospital stay after pulmonary lobectomy. We reviewed our experience with intraoperative fibrin glue to determine if it reduced air leak and improved patient outcomes. METHODS: Records of patients undergoing pulmonary lobectomy for benign or malignant disease over a 4-year period (1998-2001) were reviewed. Data was collected on age, sex, pulmonary function, pulmonary pathology, use of fibrin glue, duration of chest tube drainage, length of hospital stay, and postoperative complications. RESULTS: Three hundred and sixty patients underwent lobectomy. Fibrin glue was used intraoperatively to seal air leaks in 102 of the 360 patients (study group: 102;control group: 258). Fibrin glue was used at the discretion of the surgeon, with some surgeons using it routinely. The groups did not differ in age (p=0.29), sex (p=0.42), FEV1 (p=0.57), or pathology (p=0.08). There were no differences in outcomes such as operative mortality (study: 2 of 102, control 6 of 258, p=0.85), empyema (study: 0 of 102, control: 3 of 258, p=0.55), prolonged (>7 days) air leaks (study: 10 of 20; control: 20 of 258, p=0.71), or length of hospital stay (study: 6.3+/-2.5 days, control:7.7+/-7.2 days, p=0.83). The use of fibrin glue was associated with a reduction in the duration of chest tube intubation (study: 4.1+/-3.2 days, control: 5.5+/-3.8 days, p=0.001). CONCLUSION: Patients treated intraoperatively with fibrin glue had a significantly shorter duration of chest tube intubation after pulmonary lobectomy than those treated conventionally. However, the use of fibrin glue did not significantly influence more clinically relevant outcomes such as length of hospital stay and incidence of prolonged (>7 days) air leaks.

Survival after conservative (palliative) management of pleural malignant mesothelioma.

BACKGROUND AND OBJECTIVES: Malignant mesothelioma is a lethal disease. Aggressive multimodality treatment protocols are reportedly associated with improved survival, but the apparent survival benefits may simply reflect patient selection and the variable natural history of this malignancy. Before embarking on our own protocol of experimental treatment for mesothelioma, we sought to identify important prognostic factors and document the survival of patients treated conservatively (with palliative intent only) in our region. METHODS: We performed a retrospective review of all patients with a diagnosis of malignant mesothelioma seen at our center between 1987 and 1999. Since curative intent treatment had not been given, we assumed that measured survival would largely reflect the natural history of the malignancy. RESULTS: There were 101 patients (80 males and 21 females). Mean age was 65 +/- 9.2 years. Symptoms of disease were present for a median time of 5 months before the diagnosis was established. The most common presenting symptoms were dyspnea (46 patients), chest pain (30 patients), and weight loss (22 patients). Sixty-eight patients (68%) had a history of asbestos exposure. Mesothelioma subtypes included epithelial (43 patients), sarcomatous (26 patients), mixed (19 patients), desmoplastic (4 patients), and unspecified (9 patients). All 101 patients were treated with palliative intent. Talc pleurodesis was performed in 70 patients. At the time of analysis, 90 patients had died and 11 remained alive. Median survival was 213 (95% CI 137-289) days. Survival for the three major histological subtypes was significantly different (log rank, P = 0.0016). Histological subtype (epithelial favorable) was the only significant independent prognostic factor (Cox proportional hazard regression, P = 0.0009). CONCLUSIONS: Patients with epithelial mesothelioma survive longer than those with other histological subtypes. Conservatively managed patients with pleural malignant mesothelioma have a median survival of approximately 7 months. These data from conservatively treated patients can serve as baseline information for future studies of experimental treatments.

Self-inflicted pneumothoraces.

Self-inflicted pneumothoraces are rare manifestations of psychiatric illness. Two patients with self-inflicted pneumothoraces are reported, and the typical clinical features of factitious disorders are described. If thoracic surgeons are aware of these conditions, inappropriate surgery- and poor outcomes-can be avoided.

Prophylactic intracavitary (pneumonectomy space) antibiotic instillation: a comparative study.

BACKGROUND AND OBJECTIVES: Postpneumonectomy empyema is a dreaded complication of pneumonectomy. The effectiveness of prophylactic intracavitary antibiotic instillation is not known. We conducted a retrospective review to assess the effect of pneumonectomy space antibiotic instillation on septic complications (empyema and bronchial fistula) of pneumonectomy. METHODS: Ninety-three consecutive patients underwent pneumonectomy at our institution over a three-year period. Their charts were reviewed retrospectively and data was collected on age, gender, diagnosis, intravenous antibiotics, intracavitary (pneumonectomy space) antibiotics, empyemas, bronchial fistulas, length of hospital stay, and operative mortality. RESULTS: All 93 patients received 3 perioperative doses of prophylactic intravenous antibiotics. One group (n=47) of patients also received intraoperative intracavitary instillation of an antibiotic solution (penicillin G: 5 million units, bacitracin: 50,000 units, gentamicin: 60 mg, in 1 litre of saline) while the other group (n=46) did not. Age, gender, diagnosis, and length of stay were not significantly different in the two groups. There were no empyemas or bronchial fistulas in the intracavitary antibiotic group. Postpneumonectomy empyemas occurred in 6 (13%) patients (empyema with bronchial fistula: 5, empyema alone: 1) that had not received intracavitary antibiotics (p=0.012). There were 4 deaths (9%) in each group (p=0.63). CONCLUSIONS: Prophylactic intraoperative intracavitary antibiotic instillation may reduce the incidence of empyemas after pneumonectomy. However, a randomized trial would be needed to prove the effectiveness of this form of prophylactic antibiotic strategy.

Factors that affect the occurrence of fumonisin.

The two important Fusarium ear rots of corn, Gibberella ear rot (Fusarium graminearum, formally F. moniliforme and allied species) and Fusarium ear rot (F. verticillioides and allied species) grow under different environmental conditions. F. graminearum grows well only between 26 and 28 degrees C and requires rain both at silking and during disease progression. F. verticillioides grows well at higher temperatures, and ear rot and fumonisin accumulation are associated with drought and insect stress and growing hybrids outside their areas of adaptation. In southern Transkei, where esophageal cancer has been associated with the consumption of F. verticillioides and fumonisin-contaminated corn, environmental conditions favor this fungus in most years. In the nearby areas where the soils, crops, food consumption, and populations are the same and where esophageal cancer is low, temperatures are cooler and F. graminearum is favored. Although F. verticillioides is associated with a disease of corn, it may be that this fungus is a mutualistic endophyte of the plant. Perhaps because of this, breeding for resistance to Fusarium ear rot has produced inconclusive results to date. The best available strategies for reducing the risk of fumonisin contents of maize are to ensure that hybrids are adapted to the environment and to limit drought stress and insect herbivory. It may also be necessary to make use of alternative strategies such as producing hybrids that contain enzymes to degrade fumonisin as it is produced.

Local recurrence after total or subtotal esophagectomy for esophageal cancer.

Cancer recurrence is a common problem after esophagectomy for esophageal cancer. Local recurrence is especially problematic because it often negates the palliative benefit of esophagectomy. We conducted a retrospective review to assess the effect of extent of esophageal resection (subtotal or total esophagectomy) on local cancer recurrence. Seventy-four consecutive patients with esophageal cancer underwent esophagectomy at our institution over a four-year period. Their charts were reviewed retrospectively and data was collected on age, gender, histology, stage, tumor location, operation, resection margin status, anastomotic leaks, operative mortality, adjuvant therapy, cancer survival, and local recurrence. Total esophagectomy was done in 19 patients (transhiatal - 3; McKeown - 16) and subtotal esophagectomy was done in the other 55 patients (Lewis - 25; left thoracoabdominal - 30). The two groups were similar with respect to age, gender, histology, stage, anastomotic leaks, operative mortality, adjuvant therapy, and overall survival. Resection margins were positive for residual tumor in 2 out of 19 (11%) total esophagectomies and 9 out of 55 (16%) subtotal esophagectomies (p=0.42). Local recurrence occurred in 3 of 19 (16%) patients treated with total esophagectomy and 23 out of 55 (42%) patients treated with subtotal esophagectomy (p=0.04). We conclude that total esophagectomy is associated with fewer local cancer recurrences than subtotal esophagectomy. We, therefore, recommend total esophagectomy for the surgical treatment of esophageal cancer.

Anastomotic leaks after esophagectomy for esophageal cancer: a comparison of thoracic and cervical anastomoses.

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks remain a significant problem after esophagectomy for esophageal cancer. Many investigators have reported that leaks are more frequent after cervical, as opposed to thoracic, esophagogastric anastomoses. We conducted a retrospective review to assess the effect of anastomotic location (thoracic or cervical) on anastomotic leak incidence and severity. METHODS: Seventy-four consecutive patients with esophageal cancer underwent esophagectomy and esophagogastric anastomoses at our institution over a four-year period. Their charts were reviewed retrospectively and data was collected on age, gender, histology, stage, resection margin status, adjuvant therapy, cancer survival, anastomotic location, anastomotic leaks, and operative mortality. RESULTS: Cervical anastomoses were done in 19 patients and thoracic anastomoses were done in the other 55 patients. The two groups were similar with respect to age, gender, histology, stage, adjuvant therapy, and overall survival. Operative mortality for the entire group of 74 patients was 4% (3 patients). Resection margins were positive for residual tumor in 2 of 19 (11%) patients with cervical anastomoses and 9 of 55 (16%) patients with thoracic anastomoses (p=0.42). Leaks complicated 1 of 19 (5%) cervical and 9 of 55 (16%) thoracic esophagogastric anastomoses (p=0.21). Positive resection margins and anastomotic leaks were not significantly related (p=0.54). One of 9 (11%) leaks in the thoracic group proved fatal. CONCLUSIONS: In our experience cervical esophagogastric anastomoses do not have a higher incidence of leaks than thoracic anastomoses.

Open lung biopsy as an outpatient procedure.

BACKGROUND: Lung biopsies are frequently needed to diagnose diffuse interstitial lung diseases. Both limited thoracotomy (open lung biopsy) and thoracoscopy can be used for lung biopsies, but both procedures have traditionally required hospital admission. We report a series of patients that underwent outpatient open lung biopsy to show the safety and effectiveness of this practice. METHODS: We reviewed records of ambulatory, nonoxygen dependent patients with a clinical diagnosis of diffuse interstitial lung disease that underwent outpatient open lung biopsy between January 1997 and December 1999. All procedures were done by a senior surgeon using single lumen endotracheal anesthesia, a small anterolateral thoracotomy without rib spreading, stapled wedge resection, and no chest tube. Patients were discharged the same day. RESULTS: Thirty-two patients with a clinical diagnosis of diffuse interstitial lung disease underwent outpatient open lung biopsy. Mean age was 58 years (range, 21 to 74 years). Preoperative forced expiratory volume in 1 second was 74.3%+/-7.0% of predicted. A pathologic diagnosis was established in all patients: usual interstitial pneumonia, 26 patients; sarcoidosis, 2; metastatic carcinoma, 2; desquamative interstitial pneumonia, 1; and mixed dust pneumoconiosis, 1 patient. No patient required a chest tube, overnight observation, or hospital admission. No complications occurred. CONCLUSIONS: Selected patients with a clinical diagnosis of diffuse interstitial lung disease can safely and effectively undergo diagnostic outpatient open lung biopsy. However, careful patient selection and attention to operative detail are essential.