Clinical parameters model for predicting pathologic complete response following preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (≥60%) probability. PATIENTS AND METHODS: We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model. RESULTS: The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline (EUS)T stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662-0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643-0.728). CONCLUSION: Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR.

Adenocarcinoma of the lower esophagus with Barrett's esophagus or without Barrett's esophagus: differences in patients' survival after preoperative chemoradiation.

It remains unclear whether the overall survival (OS) of patients with localized esophageal adenocarcinoma (LEA) with Barrett's esophagus (BE) (Barrett's-positive) and those with LEA without BE (Barrett's-negative) following preoperative chemoradiation is different. Based on the published differences in the molecular biology of the two entities, we hypothesized that the two groups will have a different clinical biology (and OS). In this retrospective analysis, all patients with LEA had surgery following preoperative chemoradiation. Apart from age, gender, baseline clinical stage, location, class of cytotoxics, post-therapy stage, and OS, LEAs were divided up into Barrett's-positive and Barrett's-negative groups based on histologic documentation of BE. The Kaplan-Meier and Cox regression analytic methods were used. We analyzed 362 patients with LEA (137 Barrett's-positive and 225 Barrett's-negative). A higher proportion of Barrett's-positive patients had (EUS)T2 cancers (27%) than those with Barrett's-negative cancer (17%). More Barrett's-negative LEAs involved gastroesophageal junction than Barrett's-positive ones (P = 0.001). The OS was significantly shorter for Barrett's-positive patients than that for Barrett's-negative patients (32 months vs. 51 months; P = 0.04). In a multivariate analysis for OS, Barrett's-positive LEA (P = 0.006), old age (P = 0.016), baseline positive nodes (P = 0.005), more than 2 positive (yp)N (P = 0.0001), higher (yp)T (P = 0.003), and the use of a taxane (0.04) were the independent prognosticators. Our data demonstrate that the clinical biology (reflected in OS) is less favorable for patients with Barrett's-positive LEA than for patients with Barrett's-negative LEA. Our intriguing findings need confirmation followed by in-depth molecular study to explain these differences.

Significance of thromboembolic phenomena occurring before and during chemoradiotherapy for localized carcinoma of the esophagus and gastroesophageal junction.

Thromboembolic event (TEE) is the most common complication and a second cause of mortality in cancer patients. Multiple hypotheses for occurrence of TEE have been proposed. There are no reports on the frequency/impact of TEE in localized gastroesophageal cancer patients. We hypothesized that TEE at baseline and during chemoradiotherapy (CTRT) in gastroesophageal cancer patients would have an impact on overall survival (OS) of these patients. All consecutive patients with gastroesophageal cancer undergoing CTRT from 2001 to 2004 were eligible for this analysis. Baseline and subsequent TEEs were documented and correlated with patient characteristics and OS. One hundred ninety-eight patients were analyzed. TEEs were documented in 9.6% of the patients. At baseline, TEEs were documented in 4.0% of the patients. During CTRT, TEEs were documented in 6.1% of the patients. Pulmonary embolism (43.5%) and lower extremity venous thromboses (39%) were the most frequent TEEs. Median OS for patients with a TEE occurring at anytime was 17.7 versus 32.0 months for patients who never developed a TEE (P = 0.014). TEEs at baseline correlated with poor median survival: 13.1 versus 30.7 months for those without a TEE (P = 0.029). In a multivariable analysis, TEE at baseline and/or during CTRT was an independent predictor of OS (hazard ratio, 1.818; P = 0.040). Our data are the first to document the frequency of TEE in gastroesophageal cancer patients undergoing CTRT, and that TEE is an independent prognosticator of OS. Active research to prevent and treat TEEs is needed to improve survival of patients with localized gastroesophageal cancer.

Factors influencing recovery from and duration of lameness in Michigan (USA) horses.

The objective of this study was to identify factors that may affect recovery from and duration of a case of lameness in a stratified random sample of Michigan horses. This was done using data from Phase-II of the Michigan equine monitoring system (MEMS Phase-II), the equine health-monitoring study [Kaneene et al., Prev. Vet. Med. 29 (1997b) 277-292; Ross and Kaneene, Prev. Vet. Med. 28 (1996a) 209-224; Ross and Kaneene, Prev. Vet. Med. 29 (1996b) 59-75; Ross et al., Am. J. Vet. Res. 59 (1997) 23-29]. In this study, statistical modelling was conducted to evaluate risk factors affecting recovery from and duration of lameness using multivariable logistic regression and Cox's proportional hazards regression, respectively. Of 357 incident lameness cases reported during MEMS Phase-II, 280 (78.6%) were reported to have recovered. The median duration of a lameness case was 18 days (1st quartile (Q): 1, maximum (Max): 360). A total of 296 of 357 (82.9%) incident lameness cases received some type of treatment. Of 619 total treatments used, 329 (53.2%) were administered, conducted or applied by a veterinarian. Horses experiencing other types of lameness were less likely to recover than those experiencing hoof lameness (odds ratio (OR) = 0.48; 95% CI: 0.25, 0.93). Horses that had participated in exercise-related activities during the study period and prior to the lameness were more likely to recover (OR = 1.91; 95% CI: 1.05, 3.50). Treatment of the lameness was associated with an increased likelihood of recovery (OR = 1.82; 95% CI: 0.97, 3.45). Cases with a veterinarian involved in the diagnosis were associated with a decreased risk of recovery (OR = 0.48; 95% CI: 0.27, 0.84) and a longer duration lameness (HR = 0.58; 95% CI: 0.45, 0.73)--which might indicate that these cases were more complex or severe. Although cases treated for lameness were more likely to recover (OR = 1.82; 95% CI: 1.05, 3.50), treatment was not associated with lameness duration (HR = 0.58; 95% CI: 0.45, 0.73).

The introduction of a daily telephone advice service: how is it used and is it worth the effort?

Improving access to medical advice by telephone may reduce unnecessary consultations, limit interruptions through the day and provide a more flexible service to meet patient needs. We advertised and introduced a daily advice line for patients and found that it was used appropriately and to mutual benefit.

Survival analysis of risk factors associated with the occurrence of lameness in a Michigan horse population.

OBJECTIVE: To evaluate the associations of operation and individual animal-level risk factors with occurrence of lameness in the Michigan horse population. SAMPLE POPULATION: 3,925 horses monitored from 138 randomly selected Michigan operations for a total of 814,753 horse-days. PROCEDURE: All horses monitored < 60 days were eliminated from the source population. From the remaining horses, a prospective unmatched case-control study population was generated that included all cases and a random sample of noncases. Analysis of risk factors associated with occurrence of lameness was conducted, using Cox's proportional hazards regression model. RESULTS: Horses in larger operations, compared with horses in the first operation size quartile, were associated with decreased risk of lameness (2nd quartile [Q]: hazard ratio [HR] = 0.57; 95% confidence interval [CI]: 0.36, 0.91; 3rd Q: HR = 0.74; 95% CI: 0.49, 1.13; 4th Q: HR = 0.46; 95% CI: 0.28, 0.76). Compared with mares, stallions (HR = 1.90; 95% CI: 1.17, 3.07) and geldings (HR = 1.46; 95% CI: 1.02, 2.09) were at increased risk of lameness. Compared with horses used for breeding purposes only, those participating in exercise or performance-related activities including racing (HR = 4.70; 95% CI: 1.70, 13.03) and showing (HR = 2.80; 95% CI: 1.07, 7.28) also were at increased risk of lameness. CONCLUSIONS: Comparison of these results with those conducted using multivariable logistic regression strengthens the argument that there is decreased risk of lameness for horses in larger operations and increased risk of lameness for active horses. Additionally, results of this analysis suggested that stallions and geldings are at increased risk of lameness, compared with mares. CLINICAL RELEVANCE: Lameness prevention strategies in the horse industry should focus principally on horses participating in exercise or performance-related activities, including racing and showing, on male horses, and on horses stabled in smaller operations.

Risk factors for colic in the Michigan (USA) equine population.

A population-based prospective epidemiological study was conducted to assess risk factors for equine colic. A stratified sample of 3925 equids in 138 randomly selected equine farms in the state of Michigan was monitored in two 12-month rounds of data collection. Incidence densities were used to describe the rate of development of colic in the study population. Mortality rates, case fatality rates and survival rates were used to describe the severity of colic on the study population. Multivariable logistic regressions with random effects (grouped according to farm) were used to identify risk factors associated with occurrence of colic. A total of 3175 equids from 132 farms from the starting population of 3925 equids in 138 farms was used in the multivariable analysis. There were 77 cases of colic reported during the study period in 62 animals. Of these animals, 54 (87%) had one case, 5 (8%) had two cases, 2 (3%) had three cases, and 1 (2%) had seven cases. Of the cases reported, 49 (64%) were non-specific diagnoses, 13 (17%) impaction/acute intestinal obstruction colics, 7 (9%) spasmodic colics, 4 (5%) sand colics, 2 (3%) gas colics, 1 (1%) verminous mesenteric arteritis, and 1 (1%) enteritis due to ingestion of moldy grain. The annual incidence density of colic in the study was 3.5 cases per 100 equid-years. The surgical treatment risk was 17% (13/77). The overall mortality risk due to colic was 0.5 deaths per 100 equids, and the case fatality risk was 13% (10/77). The case fatality risk for cases treated surgically was 31% (4/13), while the case fatality risk for non-surgical colics was 10% (7/69). Risk factors associated with significantly increased likelihood of developing colic were foaling during the study, deworming during the study, increased age, and participation in showing activities. Geldings and equids provided group drinking water from sources other than tanks, buckets and automatic waterers were significantly associated with reduced risk of colic.

The Michigan equine monitoring system. II. Frequencies and impact of selected health problems.

A prospective study was designed to document the frequencies of equine health problems in the state of Michigan, USA. A total of 2469 horses from a random sample of 138 equine operations were monitored in the study in two 12-month periods: 1992-1993 and 1993-1994. All the major breeds of horses in the state were proportionately represented in the sample. Using weighted annual incidence densities as measures of disease frequencies, the 10 most frequently observed groups of health problems were (from most to least frequent) leg lameness, dermatological problems, respiratory problems, hoof and foot problems, reproductive problems, systemic problems, colic, whole body lameness, neurological problems and gastrointestinal problems (other than colic). This ranking of the top 10 health problems was different from the ranking provided by equine owners/operators at the beginning of the study. Overall, very low specific mortality rates were observed in the study. However, the conditions that were associated with mortality resulted in fairly high case fatalities. The five specific illnesses that most commonly resulted in fatalities were (from greatest to least case fatality risk) systemic problems, colic, gastrointestinal problems (other than colic), neurological problems, and foot and hoof problems. Impact of disease was evaluated in terms of average duration of a case and days lost for performance. Neurological problems, lameness and dermatological problems had the longest duration per case. Neurological problems, lameness, respiratory problems and gastrointestinal problems (other than colic) had the longest average days lost per case.

Evaluation of outbreaks of disease attributable to eastern equine encephalitis virus in horses.

OBJECTIVES: To evaluate outbreaks of disease attributable to eastern equine encephalitis virus (EEEV) in horses in Michigan, and the associated environmental patterns and weather conditions, so that factors could be identified that may have predisposed horses in specific areas of the state to infections with EEEV. DESIGN: Epidemiologic retrospective records analysis. ANIMALS: Data on EEEV vectors, wild-bird reservoir hosts, and incidental hosts, including horses and human beings, obtained from census reports and medical records compiled between 1942 and 1991. PROCEDURE: Patterns detected during outbreaks of disease attributable to EEEV infections in horses were compared to associated water drainage patterns, distributions of EEEV vectors, wild-bird reservoir and incidental hosts, and weather conditions. RESULTS: Michigan has all of the elements required to sustain EEEV on a state-wide basis. Outbreaks of disease attributable to EEEV in horses have recurred in a similar regional distribution in Michigan. Regions of Michigan that have specific patterns for water drainage, specific mosquito species, and areas with higher than expected amounts of precipitation have been associated with outbreaks of disease attributable to EEEV in horses. CLINICAL IMPLICATIONS: Evaluation of environmental patterns, weather conditions, and vector and reservoir host distributions may be useful to identify areas in Michigan and elsewhere in which horses and human beings are at increased risk for an outbreak of disease attributable to EEEV.

Gunshot wounds to the extremities in children and adolescents.

Thirty-seven patients from 8 months to 17 years of age were evaluated prospectively and retrospectively after sustaining gunshot wounds to the extremities. This review supports the belief that higher velocity weapons and shotgun-wound injuries cause greater morbidity, with increased length of hospital stay and increased cost of care. Late growth abnormalities were related to recognized initial physeal injury and not to unrecognized physeal injury. Immediate neurologic deficits usually resolved partially or fully, without surgical treatment.

Premedication for upper gastrointestinal endoscopy.

Premedication is not essential to endoscopy but patient tolerance is clearly improved and, thus, ease of examination. Although comparable results can be achieved through nonpharmacologic means, the time and effort involved precludes their widespread use. Despite near universal utilization of premedication in endoscopy, the associated risk is difficult to determine from the available literature. The reported data reveal nominal risk yet must be viewed as minimums. The ideal drug with predictable clinical effects, minimal postprocedure impairment, little respiratory compromise, and proven antagonist is not yet available. Although midazolam seems to represent an advance, recent emphasis on respiratory depression is particularly troublesome. Studies evaluating various agents have suffered from lack of quantitation of such parameters as patient tolerance, ease of examination, and postprocedure impairment. Development of proven standards for these parameters would have to occur before a definitive double-blind randomized trial could be undertaken. Suggested means of assessing these parameters are listed in Table I. Improvement in major morbidity would be difficult in light of its low incidence. As the search for the ideal drug continues, endoscopists must continue to use drugs whose full effects are incompletely understood. The ability to increase patient comfort must be balanced with the small, but ever present, risk of morbidity and mortality.

Ethanol-induced lipid peroxidation: potentiation by long-term alcohol feeding and attenuation by methionine.

Lipid peroxidation has been incriminated in some types of drug-induced liver injury, but it is unclear whether it contributes to or is present in alcoholic liver injury. In order to study this question, hepatic lipid peroxidation (measured as formation of diene conjugates) and hepatic GSH were assessed in baboons and rats after short- and long-term ethanol administration. Compared to controls, baboons fed alcohol for 1 to 4 years (chronic administration) had increased hepatic diene conjugates (16.9 +/- 4.8 OD/gm of liver) and depressed GSH (3.8 +/- 0.6 VS. 6.3 +/- 0.8 mumol/gm of liver; p less than 0.01) after an overnight withdrawal from ethanol. Administration of 1.6 gm/kg ethanol over 6 hr (acute administration) increased diene conjugates (17.6 +/- 4.3) and decreased GSH (3.2 +/- 0.5; p less than 0.01) in control animals and had an even greater effect in animals chronically fed alcohol (diene conjugates 48.5 +/- 9.2; GSH 1.8 +/- 0.3; p less than 0.001). In six rats fed alcohol for 5 to 6 weeks (chronic administration), an increase in diene conjugates was detected in microsomes (0.343 +/- 0.210 OD/mg of lipid) and mitochondria (0.143 +/- 0.061), accompanied by decrease in arachidonic acid and C22 polyenes, after acute ethanol administration (3 gm/kg p.o.) but no significant change in GSH. Simultaneous administration of methionine attenuated diene conjugate formation (0.107 +/- 0.058 and 0.035 +/- 0.020 OD/mg of lipid, respectively) and fatty acid changes. Thus chronic alcohol feeding potentiates lipid peroxidation produced by an acute dose of ethanol; these changes are not dependent on GSH depression but may be potentiated by it.

Attenuation of the ethanol-induced hepatic redox change after chronic alcohol consumption in baboons: metabolic consequences in vivo and in vitro.

Acute ethanol administration results in increased hepatic NADH/NAD+ ratio and inhibition of galactose elimination, tricarboxylic acid cycle activity, and fatty acid oxidation. To determine how this redox change is affected by chronic alcohol consumption and to assess the resulting metabolic consequences, we studied baboons which were fed alcohol as 50% of their total calories. Redox changes were evaluated through measurement of galactose elimination in vivo and lactate/pyruvate ratios in liver slices in vitro. The metabolic consequences of these changes were assessed through measurement of CO2 production and fatty acid oxidation in liver slices and hepatic lipid accumulation. Chronic alcohol feeding resulted in attenuation of inhibition of galactose elimination, increase in the lactate/pyruvate ratio, and decrease in fatty acid oxidation which were caused by acute ethanol administration. These metabolic adaptations were associated with reduced accumulation of hepatic fat.