Ross M. Bremner

Concentration of refluxed acid and esophageal mucosal injury.

The hallmark of gastroesophageal reflux disease (GERD) is an increase in esophageal exposure to gastric juice. This exposure can result in complications such as esophagitis, stricture, and Barretts esophagus. The aim of this study is to determine if there are specific pH exposure patterns that are associated with the development of these complications. The 24-hour esophageal pH data for 50 normal subjects and 154 patients with proven GERD were analyzed for time spent at different pH intervals. Increased esophageal acid exposure at a given interval occurred when the cumulative time of exposure exceeded the 95th percentile of that measured in the 50 normal subjects for that interval. The greatest prevalence of mucosal damage was found in the those patients with increased esophageal exposure to pH 0 to 2, corresponding to the known pKa of pepsin. This exposure was not related to a hypersecretory state. In addition, mucosal injury was associated with an increased esophageal exposure to pH 7 to 8. We conclude that mucosal injury in patients with GERD is related to the exposure time to gastric juice with a pH of less than 2 or greater than 7.

Lung cancer and cyclooxygenase-2

Lung cancer is by far the leading cause of cancer-related death. Overall survival is poor and has not improved substantially over the last half century. It is clear that new approaches are needed and these should include prevention, screening for early detection, and novel treatments based on our understanding of the molecular biology of this disease. Recently attention has been drawn to the role of the cyclooxygenase (COX) enzyme and its involvement in tumorigenesis. Investigations have documented two isoforms, COX-1 and COX-2, encoded by different genes. COX-1 is constitutively expressed in most tissues and appears to be responsible for the production of prostaglandins mediating normal physiologic functions, such as the maintenance of gastric mucosa and regulation of renal blood flow. In contrast, COX-2 is normally undetectable in most tissues, and is induced by cytokines, growth factors, oncogenes, and tumor promoters. A growing body of evidence indicates COX-2 plays a key role in lung cancer, and can serve as a potential marker of prognosis in this disease. Furthermore, the recent availability of COX-2 inhibitor medications offers a unique opportunity to interfere with the development of lung cancer and the progression of metastasis. Because COX-2 inhibitors have been demonstrated to interfere with tumorigenesis, the COX-2 enzyme may be an attractive target for therapeutic and chemoprotective strategies in lung cancer patients.

A Decade of Living Lobar Lung Transplantation: Perioperative Complications after 253 Donor Lobectomies†

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long‐term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for ≥14 d for persistent air leaks and/or drainage. Right‐sided donors were more likely to have a perioperative complication than left‐sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live

The effect of symptoms and nonspecific motility abnormalities on outcomes of surgical therapy for gastroesophageal reflux disease

The outcome of Nissen fundoplication in patients with a nonspecific motility abnormality compared with the outcome in patients with normal motility is unknown. One hundred consecutive patients who underwent primary Nissen fundoplication were evaluated before and a median of 50 months after operation, with emphasis on the presence of a preoperative motility disorder and its relationship to preoperative and postoperative symptoms. Compared with patients who had normal motility, patients with a nonspecific motility abnormality had a greater prevalence and severity of heartburn and regurgitation before operation. These patients also had a greater esophageal exposure to gastric juice on pH monitoring as a result of poorer esophageal clearance function. The prevalence and severity of preoperative dysphagia was not related to the presence of a motility disorder. A 90% or a 95% actuarial success rate was achieved in the relief of heartburn and regurgitation over a 96-month period in patients with and without a motility abnormality. The overall actuarial success rate was 93%. Dysphagia was rarely caused or made more severe by the procedure; if present before the operation, it was relieved in most patients. The prevalence of persistent postoperative dysphagia was similar in patients with and without a motility abnormality. The success of Nissen fundoplication in properly selected patients is not affected by the presence of a nonspecific motility disorder.

Ultrasonic epithelial ablation of the lower esophagus without stricture formation. A new technique for Barrett's ablation.

AbstractBackground: The premalignant potential of Barrett’s esophagus has stimulated efforts to find a way to ablate the columnar epithelium in order to reheal the area with squamous epithelium, thus obviating the cancer risk. This study describes and evaluates a new technique using ultrasonic energy to ablate the epithelium of the lower esophagus in a porcine model. Methods: Eight young farm pigs were used to develop the technique of applying a laparoscopic Cavitron Ultrasonic Surgical Aspirator (CUSA) to the lower esophageal mucosa through an operating gastrostomy. A further 11 Yakutan minipigs then underwent CUSA epithelial ablation, followed by a laparoscopic Nissen fundoplication or postoperative acid suppression therapy. We then assessed the healing response in these subjects. Results: Optimal CUSA energy settings enabled complete ablation of the squamous epithelium with preservation of the muscularis mucosa and submucosa. The integrity of the aspirated cells was sufficient for cytological analysis. Healing occurred by squamous regeneration without stricture formation. Conclusions: The CUSA technique holds promise for complete ablation of the Barrett’s epithelium in a single setting. The unique tissue-selective nature of the ablative process allows complete mucosal reepithelialization without stricture formation.

Regional topical hypothermia of the beating heart: preservation of function and tissue

BACKGROUND Protection of the myocardium during beating heart operations is paramount. The goal of this study is to determine if regional topical hypothermia (RTH) preserves myocardial viability and function during periods of temporary coronary artery occlusion. METHODS Sixteen pigs were divided into two groups (RTH and control). Each group received 40 minutes of midleft anterior descending coronary occlusion followed by 3 hours of reperfusion. The RTH group (n = 10) received RTH and the control group (n = 6) received no cooling. Myocardial and core temperatures were measured with thermistors. Sonomicrometers and micromonameters were used to determine load independent indices of myocardial function. These indices were measured at base line, during coronary occlusion, and at 3 hours of reperfusion. The myocardium at risk and the infarct area were determined with monastral blue dye and triphenyl tetrazolium chloride staining. RESULTS The mean myocardial temperature in the risk zone during coronary occlusion was significantly less in the RTH group (29.4 degrees C +/- 5.6 degrees C versus 35.7 degrees C +/- 1.1 degrees C, p < 0.05). After 40 minutes of coronary occlusion, both the RTH group and control had a significant reduction in regional elastance (9.38 +/- 3.54 and 11.05 +/- 1.67 mm Hg/mm) compared with base line measurements (14.70 +/- 2.42 and 16.80 +/- 4.79 mm Hg/mm), p < 0.05. However, after 3 hours of reperfusion, the elastance returned to base line levels in the RTH group (15.83 +/- 3.06 mm Hg/mm) but remained significantly depressed in the control group (9.97 +/- 3.63 mm Hg/mm, p < 0.04). Myocardial necrosis as a percentage of the risk zone was significantly less in the hypothermia group (25% +/- 2% versus 62% +/- 5%, p < 0.001). CONCLUSIONS Regional topical hypothermia during isolated temporary coronary occlusion provides regional myocardial protection expressed as a return of function and decreased necrosis. Regional topical hypothermia may be clinically applicable to myocardial preservation during beating heart operations.

Normal Esophageal Body Function: A Study Using Ambulatory Esophageal Manometry

Objective:The objective of this study was to establish normative ambulatory manometric data for contractions and contraction propagation in three levels of the esophagus.Methods:Twenty-five healthy volunteers underwent simultaneous ambulatory 24 h manometry. Concomitant 24 h pH studies were performed to exclude the presence of increased esophageal acid exposure. Pressures were recorded over a complete circadian cycle while patients continued with their normal lifestyles including eating and sleeping. Data were analyzed with a software program that was previously modified and validated and that enables quantitation of contractions in terms of efficacy.Results:The frequency of contractions was lowest during sleep, was increased when awake, and was highest during meals. Contraction amplitude increased during meals, providing a greater propulsive force for bolus transport. Similarly, the prevalence of peristaltic waves varied according to different physiologic states, i.e., while eating, upright, awake, and sleeping. An increased amplitude and prevalence of peristalsis resulted in an increase in manometric efficacy during meals.Conclusions:This study provides normative data for ambulatory manometry for comparison when studying patients with disease.

Hyperinflation Resulting in Hemodynamic Collapse following Living Donor Lobar Transplantation

BILATERAL living lobar transplantation has become an established strategy to deal with the long-term shortage of suitable donor tissue for patients with end-stage lung diseases this technique has been in use at the Keck School of Medicine at the University of Southern California since 1993. We present a case in which the disparity in size between the donated lobes and the recipients thorax led to life-threatening ventilatory and hemodynamic compromise in the immediate postoperative period.

Perforating Barrett's ulcer resulting in a life-threatening esophagobronchial fistula

Perforating benign ulcer is a very rare complication of Barretts esophagus. This report presents the management of a patient with a Barretts ulcer that penetrated into the left mainstem bronchus resulting in a life-threatening bronchial esophageal fistula. This rare complication was successfully managed by using a staged surgical approach, which combined the principles used for treating benign esophagorespiratory fistulas and perforating Barretts ulcers.

Bullets and biliptysis

Biliptysis is a dramatic physical finding which suggests the presence of a direct communication (fistula) between the biliary and bronchial tree. We report a bronchial biliary fistula resulting from penetrating thoracoabdominal trauma and the use of positive-pressure ventilation to obtain initial fistula control prior to definitive surgical repair.