KTP laser ablation of Barrett's esophagus after anti-reflux surgery results in long-term loss of intestinal metaplasia. Potassium-titanyl-phosphate.

BACKGROUND: Efforts to ablate Barrett's epithelium have met with mixed results. We report the long-term follow-up evaluation of the preliminary cohort of patients who underwent thermal ablation of Barrett's epithelium with the potassium-titanyl-phosphate (KTP) laser after anti-reflux surgery. METHODS: Nine patients with intestinal metaplasia (IM) of the esophagus underwent fundoplication (7 laparoscopic Nissen, 1 laparoscopic Toupet, 1 open Nissen) between May 1993 and October 1994. Three patients had an IM less than 3 cm long (33%). One year after the operation, all the patients were symptom free, had discontinued medications, and had a normal 24-h pH study. From June 1995 to February 1996, these patients underwent a median of two (range, 1-5) endoscopic procedures with directed mucosal ablation using the KTP laser. A comparative cohort of 21 patients (IM length, <3cm; 38%) treated during the same period with fundoplication alone served as a control. The patients were followed prospectively with annual or biennial endoscopy and biopsy. All the patients were contacted by mail, telephone, or clinic visit annually to determine symptomatic and quality-of-life outcome of antireflux surgery. RESULTS: The mean follow-up period was 6.8 years (range, 6-7.5 years). At this writing, the study patients are alive and well. Eight of the patients have experienced histologic loss of IM (89%) according to their last biopsy result. One patient has had regression of low-grade dysplasia to IM. The patients treated with fundoplication alone had a mean follow-up period of 5.6 years (range, 4.7-7.2 years). On the basis of the last biopsy result, 7 of 21 patients (33%) had no evidence of IM. CONCLUSIONS: A program of tailored antireflux surgery followed by thermal mucosal ablation causes a loss of IM in a majority of patients with Barrett's esophagus. This may represent a significant improvement in histologic outcome over that of treatment with fundoplication alone (p = 0.007 Fisher's exact test).

ENT manifestations of gastroesophageal reflux.

Reflux laryngitis is a common disease and is probably only one of several laryngeal manifestations associated with GERD. The hypothesis that GER causes laryngeal symptoms and conditions remains to be definitively proved. In many patients, the cause of laryngeal symptoms may well be multifactorial, and to identify definitively those patients in which GER may be playing a role remains a challenge. Documentation of GER using 24-h pH monitoring may assist in identifying such patients. Pharyngeal pH probe monitoring, although not without limitations, may be the optimal method to evaluate such patients in terms of documenting the presence of EPR. A suggested algorithm based on the available data in evaluating and treating patients with suspected reflux laryngitis is shown in Figure 5. First, rule out other causes of hoarseness and laryngitis. An ENT consultation is appropriate for hoarseness present >4 wk. Second, empirically treat with PPIs b.i.d. for 2-3 months, as esophageal and pharyngeal pH monitoring is costly, not readily available, time consuming, and not sensitive in making the diagnosis of GERD related laryngitis. If the patient improves after 2-3 months, therapy should be stopped and the patient observed. If symptoms recur, reinstitution of the PPI at the lowest possible dose or with use of an H2RA to maintain remission should be initiated. Third, if no improvement is noted, the patient should undergo 24-h pH monitoring with an esophageal and, if possible, a pharyngeal probe if the diagnoses of GERD and EPR are still in question. In patients in whom there is a high suspicion for GERD, pH monitoring should be performed on PPI therapy to determine whether acid suppression is adequate. A pH probe should be placed in the stomach if the question to be answered is whether 1) the PPI regimen is maintaining a pH of >4, or 2) if the addition of a bedtime H2RA maintains nocturnal intragastric pH of >4 (52-56). Patients with a completely normal pH study who are on no medications should be referred back to the ENT physician for further evaluation, as other risk factors for chronic laryngitis such as voice overuse may benefit from concomitant voice therapy. If upright reflux is the predominant reflux pattern, increasing the b.i.d. PPI dose is reasonable; but if nighttime supine reflux is predominant, recent literature suggests that the addition of a bedtime H2RA will suppress nocturnal acid breakthrough. There are, however, no long-term studies with the PPI plus H2RA regimen that document persistent nocturnal acid suppression and that show clinically significant differences in patients with nocturnal acid breakthrough. Surgery should be cautiously considered for patients who are unresponsive to PPI therapy and who have documented or undocumented evidence of GERD or EPR. The body of experience concerning GERD and the extraesophageal manifestations of GERD suggests that patients who do not respond to adequate PPI acid suppression will do poorly after antireflux surgery.

Therapeutic options in patients with Barrett's esophagus.

The rising incidence of esophageal adenocarcinoma has focused attention on the only known risk factor: Barrett's esophagus. Practice guidelines for the diagnosis, surveillance and management of Barrett's esophagus were published recently. Although the ultimate goal in the management of this premalignant condition would be the permanent elimination of Barrett's mucosa, current therapeutic options are limited or still in the investigational stages. This review summarizes current medical and surgical treatment options and introduces endoscopic ablative modalities currently under investigation.

Selecting an RIS: a three-phase process.

The Radiology Department at Washington County Hospital Association in Hagerstown, Maryland, recently selected and installed a radiology information system (RIS) to provide automation for a variety of functions within the department. This article summarizes this process and presents suggestions and recommendations for radiology administrators embarking on a similar project.

Prevention by melatonin of short day induced atrophy of the reproductive systems of male and female hamsters.

Male and female hamsters were exposed to natural photoperiodic and temperature conditions beginning on November 13 and groups of hamsters were necropsied either on January 15 or on April 10. Throughout the study, half of the hamsters (control hamsters) received subcutaneous implants of beeswax (25 mg) every other week while the other half received beeswax pellets containing 1 mg melatonin. Control beeswax-treated males necropsied in January had atrophic testes and accessory sex organs while the uteri of the control females were infantile in appearance. Melatonin treatment prevented the atrophic responses of the testes and accessory sex organs in males and the uteri in females. Melatonin-treated hamsters killed in January also had higher plasma levels of immunoreactive LH while in females both pituitary and plasma levels of LH were elevated after melatonin treatment. By April 10, the testes and accessory organs of control males and the uteri of control females had regenerated to the adult condition and these organs were comparable in size to those in melatonin-treated hamsters. The pituitary glands of control males contained slightly more LH and much more FSH than the pituitaries of melatonin-treated males. Melatonin-treated females necropsied in April had pituitary and plasma levels of LH and FSH similar to those in beeswax-treated females killed at the same time. The data show that chronic melatonin treatment prevents atrophy of the reproductive organs of male and female hamsters which is associated with the shortened days of the winter.

The effects of pineal indoles given late in the light period on reproductive organs and pituitary prolactin levels in male golden hamsters.

Intact and pinealectomized adult male hamsters kept in light:dark cycles of 14:10 (in hours) were given daily injections of either 25 microgram melatonin, 5-methoxytryptophol, N-acetylserotonin, or 6-hydroxymelatonin at 19.00 hours (13h after lights on). The injections were continued for 50 consecutive days. The daily melatonin injections significantly elevated body weights and depressed the growth of the testes and accessory sex organs and pituitary prolactin levels in intact hamsters. By comparison, in pinealectomized animals daily afternoon melatonin injections failed to alter body or testicular weights or pituitary prolactin levels. These findings indicate that for single injections of melatonin to be antigonadotrophic in the male hamster, the pineal must be intact. In intact animals, 5-methoxytryptophol and N-acetylserotonin slightly depressed the growth of the reproductive organs and pituitary prolactin levels, respectively. Again, these effects were negated by removal of the pineal gland. 6-Hydroxymelatonin was without influence on any of the parameters of reproduction that were measured.

Melatonin inhibition of reproduction in the male hamster: its dependency on time of day of administration and on an intact and sympathetically innervated pineal gland.

The daily s.c injection of 25 microgram melatonin (MEL) in oil into adult male hamsters at 7 p.m. (lights on 6 a.m. to 8 p.m.) for 50 days caused involution of the tests, coagulation of gland and seminal vesicles and depression in pituitary prolactin (Prl) levels. Similar injections of MEL given at 9 a.m. completely failed to cause regression of the sex organs or a depression in pituitary Prl levels. Injections of MEL in the p.m. were completely ineffective in inhibiting either the growth of the gonads and adnexa or the pituitary Prl levels if the animals had been pinealectomized. Likewise, superior cervical ganglionectomy, decentralization of the superior cervical ganglia and anterior hypothalamic deafferetation, procedures which interfere with the sympathetic nerve supply to the pineal gland, negated the ability of p.m. MEL injections to inhibit reproduction in male hamsters. The results indicate that daily MEL injections are capable of suppressing reproductive physiology in male hamsters, but only when the indole is injected late in the light period, in this case, 13 h after light on. The findings also illustrate that daily p.m. MEL injections can inhibit reproduction only in animals that have an intact and sympathetically innervated pineal gland.

Melatonin-pineal relationships in female golden hamsters.

Light deprivation by blinding in female hamsters was followed by a regression of the reproductive organs, an elevation of pituitary LH concentration and a depression of pituitary prolactin levels. Pinealectomy negated almost completely the effects of light deprivation on the neuroendocrine-reproductive axis. Weekly subcutaneous implants of a melatonin:beeswax pellet completely prevented the pineal gland from inhibiting reproductive physiology in blinded hamsters. The findings suggest that melatonin is not pineal antigonadotrophic factor in female golden hamsters. Melatonin implanted hamsters also had higher than normal levels of plasma prolactin.

Studies on the minimal dosage of melatonin required to inhibit pineal antigonadotrophic activity in male golden hamsters.

Blinding adult male golden hamsters was followed by atrophy, within 12 weeks, of the testes and accessory sex organs (seminal vesicles and coagulating glands) and by a significant reduction in pituitary prolactin levels. In experiment 1 blind hamsters received subcutaneously implanted melatonin-beeswax (1:24 mg) pellets at the following intervals: once per week, per 2, 3, 4, 6 weeks, or only one pellet during the 12-week experimental period. The melatonin-beeswax pellets, regardless of the frequency of implantation, overcame completely the inhibitory effects of blinding on reproduction and nearly completely the depressant action of light deprivation on pituitary prolactin levels. In the second study the melatonin-beeswax pellets were implanted subcutaneously into blind hamsters every 2 weeks. The pellets contained either 1 mg, 500, 100, 50, or 1 mug melatonin. With the exception of the 1-mug dosage, melatonin again negated almost totally the inhibitory action of darkness on the gonads and accessory organs and also, for the most part, prevented the drop in pituitary prolactin levels. Based on these studies, when melatonin is chronically administered subcutaneously in a beeswax pellet the minimal dosage of melatonin required to counteract the inhibitory effect of darkness on reproduction seems to be less than 3.6 mug/day. The effects of chronic melatonin treatment are similar to those of pinealectomy.

PIP: The minimal dosage of melatonin required to inhibit pineal antigonad otropic activity was ascertained in blinded male golden hamsters. Blinding caused a significant reduction, within 12 weeks, of testicular and accessory sex organ weights (p less than .001), as well as pituitary concentrations of prolactin (p less than .001). Subcutaneous implants of melatonin-beeswax, in a dose of 1:24 mg, completely overcame the effects of blinding on reproductive function, and almost completely overcame the depressant effect of light deprivation, regardless of the frequency of implantation. Except for a 1 mcg dose, 50, 100, 500 mcg, and 1 mg melatonin produced similar results, and almost completely blocked the decrease in pituitary prolactin concentrations. It appears that the minimal dose of melatonin required to counteract the effects of darkness on reproductive function in male golden hamsters is less than 3.6 mcg/day. Pinealectomy produced results similar to those of chronic melatonin treatment.