Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer.

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

Purification of recombinant human and Drosophila septin hexamers for TIRF assays of actin-septin filament assembly.

Septins are guanine nucleotide-binding proteins that are conserved from fungi to humans. Septins assemble into heterooligomeric complexes and higher-order structures with key roles in various cellular functions including cell migration and division. The mechanisms by which septins assemble and interact with other cytoskeletal elements like actin remain elusive. A powerful approach to address this question is by cell-free reconstitution of purified cytoskeletal proteins combined with fluorescence microscopy. Here, we describe procedures for the purification of recombinant Drosophila and human septin hexamers from Escherichia coli and reconstitution of actin-septin coassembly. These procedures can be used to compare assembly of Drosophila and human septins and their coassembly with the actin cytoskeleton by total internal reflection fluorescence microscopy.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's dysplasia: results of the National Cryospray Registry.

Retrospective series have shown the efficacy of endoscopic spray cryotherapy in eradicating high-grade dysplasia (HGD) in Barrett's esophagus (BE); however, prospective data are lacking, and efficacy for low-grade dysplasia (LGD) is unclear. The aim of this study was to assess the efficacy and safety of spray cryotherapy in patients with LGD or HGD. A multicenter, prospective open-label registry enrolled patients with dysplastic BE. Spray cryotherapy was performed every 2-3 months until there was no endoscopic evidence of BE and no histological evidence of dysplasia, followed by surveillance endoscopies up to 2 years. Primary outcome measures were complete eradication of dysplasia (CE-D) and complete eradication of all intestinal metaplasia (CE-IM). Ninety-six subjects with Barrett's dysplasia (67% HGD; 65% long-segment BE; mean length 4.5 cm) underwent 321 treatments (mean 3.3 per subject). Mean age was 67 years, 83% were male. Eighty patients (83%) completed treatment with follow-up endoscopy (mean duration 21 months). In patients with LGD, rate of CE-D was 91% (21/23) and rate of CE-IM was 61% (14/23). In HGD, CE-D rate was 81% (46/57) and CE-IM was 65% (37/57). In patients with short-segment BE (SSBE) with any dysplasia, CE-D was achieved in 97% (30/31) and CE-IM in 77% (24/31). There were no esophageal perforations or related deaths. One subject developed a stricture, which did not require dilation. One patient was hospitalized for bleeding in the setting of non-steroidal anti-inflammatory drug use. In the largest prospective cohort to date, data suggest endoscopic spray cryotherapy is a safe and effective modality for eradication of BE with LGD or HGD, particularly with SSBE.

Use of graft flow measurement and computerized tomography angiography to evaluate patency of endoscopically harvested radial artery as sequential graft in coronary artery bypass surgery.

AIM: Endoscopic radial artery (RA) graft harvesting in coronary artery bypass surgery (CABG) is attractive but concern remains regarding early graft failure. We evaluated RA graft patency via intraoperative graft flow measurements and mid-term computerized tomography angiography (CTA). METHODS: The patients who had RA harvested by endoscopic technique which was used as sequential grafts were retrospectively reviewed. Graft quality was confirmed by intraoperative transit time flow measurements. Graft stenosis was defined as stenosis >70% on CTA, 6-12 months postoperatively. RESULTS: From 2007 to 2011, 58 patients underwent endoscopic RA harvesting for sequential bypassed grafts. All received total arterialized grafts, including 22 (38%) bilateral internal thoracic arteries (ITAs), with 208 total bypassed grafts (mean: 3.59±0.52) and 128 RA bypassed grafts (mean: 2.21±0.35). Off-pump technique was performed in 43 (84%) of 51 isolated CABG patients. The pulsatility index of graft flow of the left, right ITA and sequential RA grafts with 2 or 3 targets were 1.8±0.7, 2±0.8, 1.9±0.4, and 1.7±0.7, respectively. There was no hospital mortality, and median intensive care unit and hospital stay was 2 and 8 days. Follow-up was completed in 57 patients, but 3 patients refused CTA due to lack of exertional angina. Stenosis of the left, right ITA, and RA grafts occurred in 1/54 (1.9%), 1/21 (4.8%), and 11/120 (9.2%). After a mean of 35.8±10.9 (median: 30.7) months follow-up, there was no late mortality and one documented myocardial infarction was reported. Age, diabetes, previous percutaneous coronary intervention, off-pump technique, RA target number, and graft flow or pulsatility index did not predict RA stenosis. Only RA grafts targeting the circumflex territory had an adverse impact. CONCLUSION: The RA of appropriately selected patients can be harvested safely by endoscopic technique and can be used as sequential grafts for CABG with satisfactory outcomes. Intraoperative flow measurement can assure the quality of the grafts. CTA is a valuable tool for patency follow-up.

Associations between gout tophus and polymorphisms 869T/C and -509C/T in transforming growth factor beta1 gene.

OBJECTIVES: To investigate the associations between gout tophus and polymorphisms 869T/C and -509C/T in TGF-beta1 gene. METHODS: The polymorphisms 869T/C and -509C/T were determined in 73 gout patients and 114 healthy controls among male Taiwanese using the PCR-restriction fragment length polymorphism method. Each patient was matched with 1-2 controls by age within 1-2 yrs. The tophus number was measured from all the patients' arms and legs. RESULTS: Neither 869T/C nor -509C/T showed a significant association between patients and controls in the proportions of genotypes, allele frequency or dominant and recessive models. The mean number of tophi for all patients was 1.53 +/- 3.44, showing a significant difference in distribution among the genotypes at polymorphism 869T/C (P = 0.006), but not those in polymorphism -509C/T (P > 0.05). Those carrying genotype CC at polymorphism 869T/C have a mean number of tophi 0.35 (+/- 1.11), which is significantly lower than those carrying genotype TT (3.73 +/- 4.67; P < 0.05). Those with genotype TT at polymorphism 869T/C also had 11.06 times the likelihood of having at least one tophus compared with the genotype CC after adjustment of hyperuricaemia (95% CI = 1.84, 66.36; P = 0.009). However, except for the tophus number, these two polymorphisms did not show any significant association with the clinical characteristics or biochemical markers. CONCLUSIONS: The polymorphism 869T/C in TGF-beta1 gene has a significant association with the occurrence of tophus in gout patients.

Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma.

Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 +/- 24.1 vs 58.4 +/- 65.4 IU/L, P = 0.006) and HBV DNA levels (log(10) titre: 4.20 +/- 1.33 vs 4.80 +/- 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log(10) titre: 4.79 +/- 1.34 vs 3.27 +/- 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075-2.333] rather than in young patients (OR 0.848, 95% CI 0.645-1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC.

Versatile use of extra-corporeal life support to resuscitate acute respiratory distress patients.

Extra-corporeal life support (ECLS) has been applied successfully to congenital respiratory defects but less optimally to acquired pulmonary failure. We extended this support to certain extreme complexities of patients with acute respiratory distress. From January 2003 to June 2005, 16 (nine men and seven women) patients refractory to ventilator support were treated with ECLS. Their median age was 32.4 years (1.5-70). The triggering events were pulmonary haemorrhage (n = 4), pneumonia (n = 7), aspiration (n = 2) and pancreatitis (n = 3). The indications for support were hypoxaemia in 13 and hypercapnia in three patients. Ten (63%) met the criteria of fast entry. Thirteen (81%) received veno-venous (V-V) mode support and the other three received veno-arterial mode support initially, but then converted to V-V mode after sufficient oxygenation stabilised haemodynamics. Initial pump flow was maximised to improve (mean 3250 +/- 1615 ml/min) to improve the oxygenation. Four patients with active pulmonary haemorrhage were heparin free in the first 12-24 h of support without complications. Excluding one prematurely terminated patient because of brain permanent damage, the duration of support was 162 +/- 95 h (67-363). Eleven (69%) weaned successfully from ECLS and 10 (63%) discharged and regained normal pulmonary performance in a median of 26.8 months follow-up. Pulmonary support using ECLS was feasible in selected patients with acute respiratory distress. Modification of guidelines for liberal use, early deployment before secondary organ damage and prevention of complications during support were the key to final success.

Visceral artery aneurysm: risk factor analysis and therapeutic opinion.

OBJECTIVES: To identify independent risk factors for visceral artery aneurysms. METHODS: Retrospective medical record review over 10 years. RESULTS: There were 26 men and 15 women, median age of 54 (range 22 to 85), and median follow-up was 20.6 months (range 0 to 94 months). There were 11 splenic, 17 hepatic, 8 gastroduodenal, 6 pancreatoduodenal, 5 superior mesenteric, and two inferior mesenteric artery aneurysms. Thirteen patients (13/41, 31.7%) were treated surgically without adjuvant endovascular intervention. Nineteen patients (19/41, 46.3%) were treated exclusively using endovascular procedures. Five patients (5/41, 12.2%) received second endovascular or surgical treatment as salvage procedure after the first procedure failed. Concomitant malignancy was positive predictors for in-hospital death. Renal failure, chronic lung disease, liver cirrhosis, previous abdominal surgery and concomitant malignancy were positive predictors of 2-year mortality. With the intention to treat in the whole cohort, less than 10% (2/21) of the endovascular treatments failed, compared to 18.5% (3/16) in the surgical group. Patients treated by surgery without aid of endovascular intervention, have lower 2-year mortality. In hospital-death rate was 9.8%, while overall mortality rate was 21.9%. CONCLUSIONS: The endovascular intervention provides compatible, even better early postoperative outcomes for visceral artery aneurysms to surgery. Concomitant malignancy was the major determinant of visceral artery aneurysms, both in-hospital death and survival.

Mesothelial/monocytic incidental cardiac excrescences of the heart: case report and literature review.

Mesothelial/monocytic incidental cardiac excrescences (MICE) of the heart are rare benign entities that have only been diagnosed incidentally, following cardiac surgical procedure. To date, totally 35 cases have been reported in the English literature. We describe an additional case of cardiac MICE presenting with severe aortic regurgitation for aortic valve replacement in a 20-year-old Chinese male patient. On microscopic examination, the findings initially were confused with true neoplasm. However, the related gross appearance, clinical history and further immunohistochemical staining enabled an accurate diagnosis. We review the relevant literature and found that immunohistochemical staining, especially the anti-cytokeratin antibody (AE1/AE3) and KP1 (CD-68) that were used by most investigators previously, was significant while making the diagnosis, because the two components of the cells show a contrast immunoreactivity to these two makers. The pathologists should always be alert to this entity while diagnose a cardiac surgery specimen.

Concentrations of airborne culturable bacteria in 100 large US office buildings from the BASE study.

UNLABELLED: This paper presents summary statistics of airborne culturable bacteria from the US Environmental Protection Agency Building Assessment Survey and Evaluation (BASE) study. Air samples were collected with single-stage, multiple-hole, agar impactors in 100 large office buildings in 1994-1998 to obtain normative data on indoor environmental quality. Bacterial concentrations were compared by incubation temperature, location, season, and climate zone. Forty-one percent of the samples were below the 2- or 5-min detection limits (18 or 7 CFU/m3, respectively) but less than 1% were overgrown. Mesophilic bacteria (30 degrees C) accounted for >95% of culturable bacteria, both indoors and outdoors. Average concentrations were higher outdoors, except for Gram-positive cocci, which were the only group that were significantly higher indoors (39 vs. 24 CFU/m3), and Gram-negative cocci, for which both concentrations were low and the difference were not significant. Outdoor concentrations of culturable bacteria were somewhat higher in winter (194 vs.165 CFU/m3), and the two dominant outdoor groups were unknown bacteria and Gram-positive rods. Conversely, indoor concentrations were significantly higher in summer (116 vs. 87 CFU/m3), consisting primarily of unknown bacteria and Gram-positive cocci. Bacterial concentrations were within the ranges reported in previous studies of non-problem buildings, and the extreme aggregated indoor concentrations (e.g. the 90th percentile, 175 CFU/m3) of these 100 representative buildings may serve as upper bounds to develop interpretation guidelines for office environments and similar non-manufacturing workplaces in various climate zones. PRACTICAL IMPLICATIONS: The Building Assessment Survey and Evaluation (BASE) study was one of the most comprehensive investigations of indoor environmental quality in which a standardized protocol was used to measure bioaerosols in 100 typical US office buildings. The information on the indoor and outdoor concentrations of airborne bacteria in different climate zones during the heating and cooling seasons has expanded the baseline data available for interpretation of measurements from building investigations. With suggested refinements, the BASE protocol may serve as a guide for future studies of bioaerosol concentrations, building characteristics, and occupant perceptions of the indoor environment.

Concentrations of cat and dust-mite allergens in dust samples from 92 large US office buildings from the BASE Study.

UNLABELLED: The concentrations of cat (Fel d1) and dust-mite (Der f1 and Der p1) allergens were measured in 92 large office buildings in the US Environmental Protection Agency's Building Assessment Survey and Evaluation (BASE) Study (251 dust samples; one to four samples per building). Fel d1 was detected in almost all buildings and samples (91 buildings, 99%; 235 samples, 94%; range: <0.01-19 microg/g; median: 0.3 microg/g). Cat allergen exceeded 1 microg/g (a lower symptom threshold) in 56 samples (22%) from 45 buildings, but exceeded 8 microg/g (a sensitization threshold) in only two samples (1%) from two buildings. Der f1 or Der p1 was found in approximately half of all buildings and samples (63 and 70% of buildings; 45 and 51% of samples; range: <0.01-53 microg/g and <0.01-25 microg/g; median: <0.02 and 0.03 microg/g, respectively). Mite allergen exceeded 2 microg/g (a sensitization threshold) in seven samples (3%) from five buildings and exceeded 10 microg/g (a symptom threshold) in three samples (1%) from three buildings. Fel d1 concentration was significantly higher in samples collected in summer (June to September, 48 buildings), but cat allergen was not correlated with either mite allergen. Der f1, but not Der p1, concentration tended to be higher in samples collected in winter (December to April, 44 buildings), and the two mite allergens were significantly correlated only in winter. Cat and mite allergens were detected in 78% of representative US office buildings, but the concentrations seldom exceeded levels associated with sensitization or symptom provocation. PRACTICAL IMPLICATIONS: The information on the concentrations of cat and dust-mite allergens in representative large US offices has expanded the baseline data available for interpretation of measurements from other building investigations. With suggested refinements, the BASE protocol for measurement of allergen concentrations in dust samples may serve as a guide to future studies of building characteristics, bioaerosol concentrations, and occupant perceptions of the indoor environment.

The role of glottal gap in predicting aspiration in patients with unilateral vocal paralysis.

Aspiration has been frequently noted among patients suffering from vocal-fold paralysis. The association between a defect of glottal closure and aspiration in patients with unilateral vocal paralysis appears to have been rarely reported. The current study reviews collected data consisting of videotaped flexible nasoendoscopy and stroboscopy for patients with a unilateral vocal-fold paralysis. Mean normalized glottal gap areas for patients suffering vocal paralysis with associated aspiration are significant greater than that for the non-aspiration group. Subsequent to the surgical correction of the glottal gap, all patients recovered well from their earlier aspiration. The investigation of objectively derived data revealed that poor airway protection due to incomplete closure of the vocal fold was the major cause of aspiration for patients suffering unilateral vocal-fold paralysis. Intracordal autologous fat injection can successfully improve the breath control and eliminate aspiration in patients with vocal-fold paralysis.

Indoor/outdoor PM10 and PM2.5 in Bangkok, Thailand.

Twenty-four-hour averaged PM10 and PM2.5 concentrations were obtained by using 4-liter-per-minute-pumps and impactors in microenvironments of a busy shopping district and a university hospital campus. In both areas, most people live directly adjacent to their worksites--minimizing the need to measure commuting exposure as part of total daily exposure. Co-located samplers were set in indoor microenvironments, the near-ambient zone of the households, and at nearby streetside central ambient monitoring stations. Smoking and use of other indoor PM sources were recorded daily via questionnaires. Consistent with previous studies, smoking and the use of charcoal stoves increased indoor particulate matter levels. The sampled air-conditioned hospital area had substantially lower particle concentrations than outdoors. A simple total exposure model was used to estimate the human exposure. The averaged ratios of co-located PM2.5/PM10 concentrations in various microenvironments are reported for each location. A single daily indoor average PM10 concentration for all households measured in a given sampling day is calculated for correlation analysis. Results showed that day-to-day fluctuations of these calculated indoor PM10 levels correlated well with near-ambient data and moderately well with ambient data collected at the nearby central monitoring site. This implies that ambient monitors are able to capture the daily variations of indoor PM levels or even personal exposure and may help explain the robust association of ambient PM levels and health effects found in many epidemiological studies. Absolute PM exposures, however, were substantially underestimated by ambient monitors in the shopping district, probably because of strong local sources.

Concurrent thrombosis of cerebral and femoral arteries in a patient with nephrotic syndrome.

Although venous thrombosis is a frequently encountered problem in nephrotic syndrome, the occurrence of arterial thrombosis is much less common, and is usually associated with a poor prognosis. To the best of our knowledge, there has been only one reported case of concurrent cerebral and femoral artery thrombosis, that of a 23-year-old male who finally died. Herein, we report a case of a 35-year-old woman with nephrotic syndrome. She developed cerebral and femoral arterial thrombosis simultaneously when the nephrotic syndrome relapsed. Immediate thrombectomy of the femoral artery, followed by anticoagulation and immunosuppressive therapy, were employed. The patient recovered completely and is now doing well. Our experience indicates that multiple artery thrombosis in nephrotic patients may not necessarily carry a poor outcome if early and aggressive treatment can be undertaken.

An Exploratory Analysis of the Relationship Between Mortality and the Chemical Composition of Airborne Particulate Matter.

We explored relationships between daily mortality and the major sources of airborne particulate matter (PM) using a newly developed approach, Factor Analysis and Poisson Regression (FA/PR). We hypothesized that by adding information on PM chemical speciation and source apportionment to typical PM epidemiological analysis, we could identify PM sources that cause adverse health effects. The FA/PR method was applied to a merged data set of mortality and extensive PM chemical speciation (including trace metals, sulfate, and extractable organic matter) in New Jersey. Statistically significant associations were found between mortality and several of the FA-derived PM sources, including oil burning, industry, sulfate aerosol, and motor vehicles. The FA/PR method provides new insight into potentially important PM sources related to mortality. For the data set we analyzed, the use of FA/PR to integrate multiple chemical species into source-related PM exposure metrics was found to be a more sensitive tool than the traditional approach using PM mass alone.

Sixteen-year experience with 1,000 heart transplants at UCLA.

1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.

Blunt trauma with flail chest and penetrating aortic injury.

Blunt chest trauma with flail chest is common. The mortality attributes initially to the associated pulmonary contusion, massive hemothorax and later to the occurrence of adult respiratory distress syndrome. We report a case of flail chest with segmental fractures near the costovertebral junction and delayed hemothorax attacked 14 h later. The final diagnosis of the penetrating aortic injury by detached rib fragment was appreciated by aortogram. Unfortunately, active aortic hemorrhage made prompt thoracotomy in vain for life salvage.

Totally minimally invasive cardiac surgery for coronary artery disease.

OBJECTIVE: We report our experience using minimally invasive techniques both to perform coronary artery bypass and harvesting of saphenous vein grafts in 25 patients with left main or triple vessels disease. METHODS: From March 1997 to June 1997, 25 patients received elective coronary artery bypass grafting using minimally invasive surgical techniques for left main or triple vessels disease. Saphenous vein grafts were harvested using minimally invasive techniques under direct vision. The coronary artery bypass grafting was performed through a limited left anterior parasternal minithoracotomy under femoro-femoral or aorto-atrial cardiopulmonary bypass. The myocardium was protected by antegrade infusion of cold blood cardioplegic solution while the aorta was cross-clamped. RESULTS: Three to four distal anastomoses were performed with the saphenous vein graft and the left internal thoracic arterial graft. The aortic cross-clamp time was 60-135 min. The duration of cardiopulmonary bypass was 89-172 min. The postoperative course was uneventful for all patients. All patients were found to be in New York Heart Association functional class I or II on follow-up from 3-7 months after surgery. CONCLUSIONS: Minimally invasive coronary artery surgery is technically feasible and can be performed in left main or triple vessel disease safely and effectively for complete revascularization.