An increased proportion of inflammatory cells express tumor necrosis factor alpha in idiopathic achalasia of the esophagus.

Achalasia is a motility disorder characterized by the absence of coordinated peristalsis and incomplete relaxation of the lower esophageal sphincter. The etiology remains unclear although dense inflammatory infiltrates within the myenteric plexus have been described. The nature of these infiltrating cells is unknown. The aim of this study was to evaluate the expression of proinflammatory cytokines - namely, tumor necrosis factor alpha and interleukin-2 - in the distal esophageal muscle in patients with achalasia. Lower esophageal sphincter muscle from eight patients undergoing myotomy or esophagectomy for achalasia of the esophagus were obtained at the time of surgery. Control specimens consisted of similar muscle taken from eight patients undergoing operation for cancer or Barrett's esophagus. The expression of tumor necrosis factor alpha and interleukin-2 were assessed by immunohistochemistry. The total number of inflammatory cells within the myenteric plexus were counted in five high power fields. The percentage of infiltrating cells expressing tumor necrosis factor alpha or interleukin-2 was calculated. Clinical data including demographics, preoperative lower esophageal sphincter pressure, duration of symptoms, and dysphagia score (1 = no dysphagia to 5 = dysphagia to saliva) were obtained through electronic medical records. Statistical comparisons between the groups were made using the unpaired t-test, Fisher's exact test, or Mann-Whitney U test, with a two-tailed P-value less than 0.05 being considered significant. The total number of inflammatory cells was found to be similar between the groups. A significantly higher proportion of inflammatory cells expressed tumor necrosis factor alpha in achalasia as compared with controls (22 vs. 11%; P= 0.02). A similar percentage of infiltrating cells expressed interleukin-2 (40 vs. 41%; P= 0.87). Age, gender, preoperative lower esophageal sphincter pressure, or dysphagia score were not correlated to expression of these cytokines. There was, however, a significant inverse correlation between duration of symptoms and the proportion of inflammatory cells expressing tumor necrosis factor alpha in achalasia (P= 0.007). In conclusion, a higher proportion of infiltrating inflammatory cells expressed tumor necrosis factor alpha in achalasia. Furthermore, this proportion appears to be highest early in the disease process. Further studies are required to more clearly delineate the role of tumor necrosis factor alpha in the pathogenesis of this idiopathic disease.

Stereotactic radiosurgery for lung cancer.

Lung cancer is the most common cause of cancer death in both men and women in the United States. Anatomic lobectomy is the standard treatment and offers the best results for curative treatment of early stage non-small cell lung cancer (NSCLC). With an aging population, a significant proportion of patients are not surgical candidates at the time of diagnosis. In medically inoperable patients, standard external beam radiation has been offered as treatment, with suboptimal results. Stereotactic radiosurgery (SRS), a term coined by Leksell describes an approach using multiple convergent beams, precise localization with a stereotactic coordinate system, and rigid immobilization. It provides precise delivery of beams from multiple collimated paths which maximizes radiation delivery to the tumor, and minimizes the exposure of normal tissue. Early results with SRS are very encouraging, and prospective trials are underway in our institution and others to evaluate its role in early stage NSCLC. In article we review the role of stereotactic radiosurgery for the treatment of lung cancer.

A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy.

OBJECTIVE: Esophagectomy may lead to impairment in gastric emptying, unless a pyloroplasty or pyloromyotomy is performed. These procedures may be technically challenging during minimally invasive esophagectomy, and they are associated with a small but definable morbidity, such as leakage and dumping syndrome. We sought to determine the results of our early experience with injecting the pylorus with botulinum toxin instead of conventional pyloric drainage. METHODS: Fifteen patients who had undergone esophagectomy and injection of the pylorus with botulinum toxin were identified. Twelve patients had undergone botulinum toxin injection at the time of minimally invasive esophagectomy, and the remaining three had been treated endoscopically after surgery. The latter three patients had undergone esophagectomy with either no pyloric drainage (n = 2) or an inadequate pyloromyotomy (n = 1), and they presented in the postoperative period with delayed gastric emptying. The adequacy of emptying after injection was assessed by the patients' ability to tolerate a regular diet, a barium swallow, and a nuclear gastric emptying study. RESULTS: No patient injected with botulinum toxin during esophagectomy developed delayed gastric emptying or aspiration pneumonia in the perioperative period. Eight of these patients underwent a nuclear emptying scan at a median of 4.2 months after surgery, which showed a mean emptying half-life of 100 min. With a median follow-up of 5.3 months, one patient (8%) required reintervention for symptoms of gastric stasis, presumably after the effect of the toxin subsided. All three patients injected postoperatively demonstrated an improvement in symptoms of gastric outlet obstruction and were able to resume a regular diet. CONCLUSIONS: Injection of the pylorus with botulinum toxin can be performed safely in patients undergoing esophagectomy. Longer-term studies are needed to clarify the efficacy and durability of this technique compared to the accepted procedures of pyloromyotomy or pyloroplasty.

Erythromycin, motilin, and the esophagus.

BACKGROUND: Motilin induces phase III activity of the gastroesophageal tract. Erythromycin has a motilin-like effect on the stomach, but possible esophageal effects have not been evaluated and are the focus of our investigation. METHODS: Esophageal manometry was performed in 11 healthy volunteers before and after intravenous infusion of 500 mg erythromycin. Values are expressed as means +/- SEM. RESULTS: Lower esophageal sphincter (LES) pressure increased from 21.1 +/- 2.6 mm Hg at baseline to 37.5 +/- 3.8 mm Hg after erythromycin infusion (p < 0.0001). Erythromycin did not affect LES length, esophageal body contraction amplitude, duration or velocity, or the upper esophageal sphincter. Serum motilin levels decreased from 96.4 +/- 10.9 pmol/L to 81.8 +/- 10.9 pmol/L (p < 0.01) after erythromycin administration. CONCLUSIONS: Erythromycin profoundly stimulates the normal human LES. This is a direct motilin agonist-like effect and is not mediated by release of endogenous motilin. Erythromycin has no important effect on the esophageal body or the upper esophageal sphincter.

Erythromycin strengthens the defective lower esophageal sphincter in patients with gastroesophageal reflux disease.

Motilin induces phase III activity of the gastrointestinal tract. Erythromycin has a motilin-like effect on the stomach and significantly increases the lower esophageal sphincter (LES) pressure in normal volunteers. This investigation was performed to evaluate the effects of erythromycin on esophageal function in patients with gastroesophageal reflux disease (GERD). Esophageal manometry was performed in 10 GERD patients before and after intravenous infusion of 500 mg of erythromycin. Values are expressed as mean +/- SEM. LES pressure increased from 13.9 +/- 2.9 mm Hg at baseline to 28.9 +/- 3.6 mm Hg after infusion of erythromycin (p < 0.01). The duration of contractions in the proximal, middle, and distal esophagus was significantly prolonged from 3.5 +/- 0.4 seconds, 3.8 +/- 0.4 seconds, and 4.1 +/- 0.5 seconds to 4.2 +/- 0.2 seconds, 4.6 +/- 0.5 seconds, and 5.6 +/- 0.6 seconds, respectively, after infusion of erythromycin (p < 0.05 for each comparison). Erythromycin did not effect esophageal body contraction amplitude or velocity, or the upper esophageal sphincter. Serum motilin decreased slightly after the administration of erythromycin. We concluded the following: (1) Erythromycin profoundly stimulates the defective LES in patients with GERD. This appears to be a direct motilin agonist-like effect rather than being mediated by release of endogenous motilin. (2) Erythromycin has less effect on the esophageal body, although it does prolong the duration of esophageal contractions.

Performance reduction in finger amputees when reaching and operating common control devices: a pilot experimental investigation using a simulated finger disability.

This paper reports results of an experimental laboratory investigation to determine if finger amputations (most pervasive upper extremity injury in the United States) result in significant work performance deterioration in tasks requiring operation of common control devices found in industrial settings. Ten male student volunteers from the University of Cincinnati participated in this study. The finger disability simulated was of an extreme nature, and was defined as the loss of four fingers in the preferred hand and the thumb in the nonpreferred hand. While being seated, participants activated 5 types of industrial control devices (a rotary dial, a push button, a toggle switch, a castor wheel, and a rocker switch). The controls were assembled on a device attached to a cylindrical pole, such that the control assembly could move up and down the cylindrical pole. The vertical height of control location (15, 20, and 30 in. from the seat reference point) and angle of control location in vertical plane (0 degree, 45 degrees, 90 degrees, and 135 degrees) were varied in the experiment. Participants also had their torso restrained or unrestrained while reaching and activating controls, in addition to the presence or absence of the simulated disability in each participant. Functional reaches and arm reaches from the wall were measured for participants in the sample to determine the distances at which to place the control pole assembly. If a participant was able to reach the control, the time taken to activate and operate the control was recorded. Overall results indicate that participants took significantly longer (p < 0.05) to activate controls in the presence of the simulated disability. Physical restraint did not significantly alter performance provided the participant was able to reach the control. The type of control and the height of location of the control also significantly affected work performance.

Obesity correlates with gastroesophageal reflux.

Thirty morbidly obese patients presenting for bariatric surgery were evaluated for symptomatic and objective evidence of gastroesophageal reflux. Sixteen patients had heartburn while 14 were asymptomatic. All underwent esophageal function testing; manometry was performed in all patients, pH monitoring in 28. Patients with esophageal pH < 4 for more than 5% of observed time weighed more than those with normal acid exposure, 165.2 vs 129.8 kg (P < 0.01), and had significantly higher body mass indices, 56.5 vs 48.3 kg/m2 (P < 0.05). Similarly, morbidly obese patients with abnormal reflux scores weighed significantly more and had greater body mass indices than patients with normal scores (P < 0.05). Lower esophageal sphincter pressure was higher in patients with normal esophageal acid exposure than in those with abnormal findings, 15.5 vs 12.5 mm Hg (P < 0.05). This study demonstrates a correlation between both weight and body mass index with gastroesophageal reflux.