Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.     

Effect of long-term treatment of two tobacco-specific N-nitrosamines on the vitamin A status of mice

The effect of long-term treatment of two important tobacco-specific N-nitrosamines, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), on the depot or circulating levels of vitamin A of Swiss and BALB/c male mice was studied. It was observed that treatment of both NNN and NNK in Swiss and BALB/c mice decreased liver vitamin A levels significantly. NNK treatment also caused a decrease in the levels of vitamin A in plasma.     

Effect of dietary protein on Masheri-induced drug metabolising enzymes

The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed.     

Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.

OBJECTIVE: Multi-vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses. METHODS: Three hundred and twenty-eight IUGR fetuses (abdominal circumference < 5th percentile, elevated umbilical artery (UA) pulsatility index (PI)) had concurrent surveillance with UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler ultrasonography and BPS (fetal tone, movement, breathing, maximal amniotic fluid pocket and fetal heart rate). Patients were stratified into three groups according to their Doppler examination: (1) abnormal UA alone; (2) brain sparing (MCA-PI > 2 SD below mean for gestational age); and (3) abnormal DV (PI > 2 SD above the mean for gestational age) and BPS groups: (1) normal (> 6/10); (2) equivocal (6/10); and (3) abnormal (< 6/10). Predictions of short-term perinatal outcomes by both modalities were compared for stratification. The distribution and concordance of Doppler and BPS test results were examined for the whole patient group and based on delivery prior to 32 weeks' gestation. RESULTS: Abnormal UA Doppler results alone were observed in 109 fetuses (33.2%), brain sparing in 87 (26.5%) and an abnormal DV in 132 (40.2%). The BPS was normal in 158 (48.2%), equivocal in 68 (20.7%) and abnormal in 102 (31.1%). Both testing modalities stratified patients into groups with comparable acid-base disturbance and perinatal outcome. Of the nine possible test combinations the largest subgroups were: abnormal UA alone/normal BPS (n = 69; 21%) and abnormal DV Doppler/abnormal BPS (n = 62; 18.9%). Assessment of compromise by both testing modalities was concordant in 146 (44.5%) cases. In 182 fetuses with discordant results the BPS grade was better in 115 (63.2%, P < 0.0001). Marked disagreement of test abnormality was present in 57 (17.4%) fetuses. Of these, abnormal venous Doppler in the presence of a normal BPS constituted the largest group (Chi-square P < 0.002). Stratification was not significantly different in patients delivered prior to 32 weeks' gestation. CONCLUSION: Doppler ultrasonography and BPS effectively stratify IUGR fetuses into risk categories, but Doppler and BPS results do not show a consistent relationship with each other. Since fetal deterioration appears to be independently reflected in these two testing modalities further research is warranted to investigate how they are best combined.     

Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.     

Chronic subdural haematoma associated with nontraumatic CSF rhinorrhea: a management challenge.

We report an unusual case of chronic subdural haematoma (CSH) associated with cerebrospinal fluid (CSF) rhinorrhoea emphasizing the importance of managing both conditions simultaneously. A 59- year-old man presented with watery discharge from the right nostril, of 2 months duration. MRI of the brain showed a CSH in the left fronto-parietal region with significant mass effect. There was an arachnoidocoele with a defect in the planum sphenoidale. He first underwent a burr hole evacuation of the CSH following which the CSF rhinorrhea did not subside, even with bed rest. Transnasal endoscopic closure of the CSF dural fistula was done. On the first post-operative day, he was disoriented and a CT scan showed a recollection of the subdural haematoma that required repeat evacuation. The patient was asymptomatic at discharge. To our knowledge this is the first reported case of CSF rhinorrhoea associated with CSH. Simultaneous closure of the CSF dural fistula at the time of evacuation of a coexisting CSH would be the optimal management.     

Implementation of a successful endovascular surgical program in a non-teaching tertiary-care centre in Ontario.

Endovascular surgical techniques have become an accepted standard of care for high-risk patients with abdominal aortic aneurysms and for certain patients with thoracic aortic pathology and peripheral arterial aneurysms. In Canada, endovascular surgery has been concentrated in tertiary-care academic teaching institutions. As the technology evolves and as expertise advances, the applicability of endovascular techniques will expand. With time, and as the demand for endovascular techniques rises, this expertise will increasingly need to be delivered by dedicated vascular surgical services in nonteaching institutions. The dissemination of endovascular surgical capabilities represent a unique challenge. We report the successful implementation of an endovascular surgical program in a tertiary-care nonteaching institution using a carefully planned preceptorship model. We review our initial 49 cases and discuss 6 factors important to the successful establishment of an endovascular surgical service: education, teamwork, strict selection of patients, use of a single stent-graft manufacturer, industry support and endovascular preceptorship. Our experience may be used as a model by other institutions in Canada.     

Receiver Operating Characteristic (ROC) to Determine Cut-Off Points of Biomarkers in Lung Cancer Patients

The role of biomarkers in disease prognosis continues to be an important investigation in many cancer studies. In order for these biomarkers to have practical application in clinical decision making regarding patient treatment and follow-up, it is common to dichotomize patients into those with low vs. high expression levels. In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of the ROC, sensitivity, specificity, as well as likelihood ratios were calculated to determine levels of growth factor biomarkers that best differentiate lung cancer cases versus control subjects. Selected cut-off points for p185^erbB-2 and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer (AUC = 89% and 90%, respectively); while AUC increased to at least 90% for selected cut-off points for p185^erbB-2 membrane, EGFR membrane, and FASE when comparing between control versus carcinoma tissues from lung cancer cases. Using data from control subjects compared to patients with lung cancer, we presented a simple and intuitive approach to determine dichotomized levels of biomarkers and validated the value of these biomarkers as surrogate endpoints for cancer outcome.     

An immunocytochemical marker for hamster retinal ganglion cells

Summary We examined the specificity and developmental time course of the labelling of retinal ganglion cells in Syrian hamsters by a monoclonal antibody AB5. In adult hamsters, AB5 selectively labelled somata in the ganglion cell layer, dendrites in the inner plexiform layer and axons in the nerve fibre layer. When retinal ganglion cells were retrogradely labelled with Dil prior to AB5 immunocytochemistry, all of the retrogradely labelled retinal ganglion cells in the ganglion cell layer were AB5 immunoreactive, indicating that AB5 labels all classes of ganglion cell in that layer. In retinae depleted of retinal ganglion cells by neonatal optic nerve transections, AB5 did not label any somata or processes, indicating that AB5 specifically labels retinal ganglion cells. During development, AB5 labelling first appeared as a weak staining of cell bodies in the ganglion cell layer on postnatal day 12 (P12; PO=first 24 h following birth) and acquired the staining pattern seen in the adult by postnatal day 14. From the onset of AB5 immunoreactivity, AB5-labelled somata of varying sizes were present across the entire retinal surface. Although AB5 labelled retinal ganglion cell axons in the nerve fibre layer of the retina it did not label the optic nerve or retinal ganglion cell axons in the brain at any age examined. AB5 labelling was also found to be compatible with bromodeoxyuridine immunocytochemistry and, therefore, useful for determining the time of generation of hamster retinal ganglion cells.