Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization

OBJECTIVES: Barrett's oesophagus is a pre-neoplastic lesion, which develops as a complication of chronic gastro-oesophageal reflux disease and predisposes the patient to oesophageal adenocarcinoma. Our aim was to characterize karyotypic changes that may occur during the progression of Barrett's metaplasia through low-grade dysplasia and high-grade dysplasia to adenocarcinoma. METHODS: The technique of comparative genomic hybridization was used to characterize genome-wide changes in biopsies from patients with low-grade dysplasia, low-grade dysplasia plus high-grade dysplasia, high-grade dysplasia or adenocarcinoma. Both fresh and archival material was examined. RESULTS: Comparative genomic hybridization revealed a large amount of widespread chromosome instability at the high-grade dysplasia stage. No significant chromosome changes were detectable by comparative genomic hybridization in patients with low-grade dysplasia. Karyotypic changes in the adenocarcinoma patients were more specific than those found in the high-grade dysplasia patients. Chromosome 4 was amplified most often in high-grade dysplasia and chromosome 8q was amplified most frequently in the adenocarcinomas. CONCLUSIONS: These data demonstrate that high-grade dysplasia is the stage exhibiting widespread chromosome instability, which is detectable by comparative genomic hybridization. This instability is undetectable in low-grade dysplasia. The chromosome variation seen at high-grade dysplasia may be the source of more specific karyotypes that progress to adenocarcinoma. Importantly, we have identified chromosome 4 amplification as being heavily involved in the initiation of Barrett's progression. Specific chromosome changes (4 and 8q) may represent important regions on which to focus attention in future studies, with a view to identifying diagnostic markers.     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.     

Modifiable risks of incident functional dependence in Hispanic and non-Hispanic white elders: the San Luis Valley Health and Aging Study

PURPOSE: This study identified modifiable risks associated with incident functional dependence, compared their effects, and estimated the percent risk attributable to each factor, by ethnicity. DESIGN AND METHODS: The prospective study cohort comprised 751 rural Hispanic and non-Hispanic White elders from southern Colorado who reported no dependence in basic and instrumental activities of daily living (ADLs and IADLs) at baseline. Logistic regression modeled the effects of physical inactivity, nutritional risk, smoking, and falls on incident disability 22 months later, with and without adjustment for baseline ADL and IADL difficulty. Population attributable risk percentages assessed these modifiable risks by ethnicity. RESULTS: Each risk factor multiplied the likelihood of incident dependence by 1.4 or more, adjusted for covariates. Attributable risk percentages ranged from 8% to 32% depending on risk factor, ethnicity, and baseline ADL and IADL difficulty status. Attributable risk was generally greater among Hispanic elders, the result of higher prevalence of most of the risk factors. IMPLICATIONS: Interventions targeted at inadequate nutrition, inactivity, smoking, and preventable falls offer opportunities to reduce incident functional disability, especially among Hispanic elders.     

Does Prior Abdominal Surgery Influence Conversion Rates and Outcomes of Laparoscopic Right Colectomy in Patients with Neoplasia?

Purpose  The study investigated the impact of prior abdominal surgery on conversions and outcomes of laparoscopic right colectomy. Methods  A consecutive series of 414 patients with cancer or adenomas who underwent a laparoscopic right colectomy from March 1996 to November 2006 were studied for surgical conversions and outcomes. Conversion was defined as an incision length > 7 cm. Results  Patients with prior abdominal surgery (n = 191) were compared with patients with no prior abdominal surgery (n = 223), and showed no significant differences in age, ASA classification, length of stay, operative time, blood loss, harvested nodes, tumor size, and specimen length. Significantly more wound infections occurred in the prior abdominal surgery group (22 vs.12, P = 0.023). Body mass index > 30 showed a three-fold increased risk of conversion. Fifteen percent of the no prior abdominal surgery patients and 17 percent of the prior abdominal surgery patients were converted (P > 0.05). Conversion was associated with a longer mean length of stay (8.8 days) relative to laparoscopically completed cases (6.3 days) regardless of prior abdominal surgery history (P < 0.0001). Conclusions  Laparoscopic right colectomy for neoplasia was not associated with a higher conversion rate or morbidity in patients with prior abdominal surgery. Prior abdominal surgery is not a contraindication to laparoscopic right colectomy. Presented at the 15th International Congress of the European Association of Endoscopic Surgery, Athens, Greece, July 4 to 7, 2007.     

A novel approach to improve undergraduate surgical teaching

Background:

Undergraduate surgery is at an important crossroads. Many departments report significant difficulties delivering effective teaching. Our student feedback indicated a dated surgical curriculum lacking structure, quality and uniformity. We report on a new ”blended” approach employing a combination of professional DVDs, case based discussions, online material and traditional bedside teaching designed to provide structure, standardization, and equality of learning .

Methods:

Year 4 students who had undertaken the new course and year 5 students who had participated in the traditional teaching programme were compared. Students completed a 20 item questionnaire about their experiences of the surgical teaching programme.

Results:

One hundred and seventy-one year 4 (70%) and148 year 5 students (66%) responded. Domains relating to “Overall Satisfaction with the course”, “Approval of innovative teaching methods and interactivity” and “Satisfaction with the clarity of course information” showed improvements when comparing the new and old programmes. However bedside teaching was not rated as highly in the new programme (p<0.05).

Conclusion:

This blended approach has resulted in improved student understanding and engagement. The apparent compromise of bedside teaching may be a reflection of higher expectations. We believe that a similar blended approach has the potential to re-invigorate surgical teaching elsewhere.     

In Vitro Activity of Ceftazidime-Avibactam against 338 Molecularly Characterized Gentamicin-Nonsusceptible Gram-Negative Clinical Isolates Obtained from Patients in Canadian Hospitals

The mechanism of aminoglycoside resistance among 338 gentamicin-nonsusceptible Gram-negative bacteria (207 Enterobacteriaceae and 131 Pseudomonas aeruginosa) was assessed, and the in vitro activity of ceftazidime-avibactam against these isolates was determined. Aminoglycoside-modifying enzymes were detected in 91.8% of Enterobacteriaceae and 13.7% of P. aeruginosa isolates. A single strain of Klebsiella pneumoniae harbored a 16S rRNA methylase (ArmA). The ceftazidime-avibactam MIC₉₀ values were 0.5 μg/ml (MIC, ≤8 μg/ml for 100% of isolates) and 16 μg/ml (MIC, ≤8 μg/ml for 87.8% of isolates) against gentamicin-nonsusceptible Enterobacteriaceae and P. aeruginosa isolates, respectively.