Regulation of distal esophageal mucosal blood flow: the roles of nitric oxide and substance P

BACKGROUND: An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. METHODS: Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. RESULTS: Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist NG-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). NG-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.1) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). CONCLUSIONS: Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.     

Laparoscopy-assisted devascularization of the lower esophagus and upper stomach in the management of gastric varices

Devascularization of the lower esophagus and the upper stomach is one method of treating patients with clinically significant gastric varices. We describe a new method of laparoscopically-assisted devascularization which has been applied in seven patients with esophagogastric varices. Three of the seven patients had an episode of gastric variceal bleeding, and the remaining four had moderate to large gastric varices with red color signs. The operative procedure was carried out without pneumoperitoneum by using an ordinary forceps and laparoscopic instruments through a small skin incision (3-5 cm); the abdominal wall was elevated with a U-shaped retractor. The operative field was obtained by laparoscopic and direct vision illuminated by laparoscopic light. The procedure time ranged from 100 to 180 minutes with minimal blood loss (70-320 g). No complications were encountered. All patients could be discharged within one week; postoperative pain was minimal and all patients returned to work early. Follow-up (mean 11.4 months) showed no recurrence of gastric varices although, due to an incomplete procedure in two cases, two patients were treated additionally by endoscopic injection of histoacryl.     

GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function

Gamma-aminobutyric acid (GABA) antagonist (bicuculline methiodide, BIC; picrotoxin, PIC) or agonist (muscimol, MUS) microinjections were made into the dorsal motor nucleus of the vagus nerve (DMV), and effects on lower esophageal sphincter pressure (LESP), gastric motility, and gastric acid secretion were determined in chloralose-anesthetized cats. Right or left DMV sites were microinjected with BIC, PIC, MUS, or isotonic tonic saline (140 nl) through a glass micropipette having a tip diameter of 15-21 microns. Esophageal body, LESP, and gastric fundic pressures were measured manometrically. Circular smooth muscle contractions of the antrum and pylorus were recorded with strain-gauge force transducers. Gastric acid secretion was measured every 15 min through a gastric cannula and titrated to pH 7.0. DMV microinjection sites were verified histologically. Direct BIC microinjections (0.275 or 0.550 nmol) into the DMV primarily produced a decrease in LESP (71% of all sites tested), with mean LESP changing from 23.2 +/- 1.7 mmHg to 3.7 +/- 0.7 mmHg (p < 0.01). Tonic LESP increases and phasic LESP contractile activity occurred less frequently. BIC-induced LESP responses were abolished by vagotomy or by microinjections of MUS (0.5 to 10 nmol) into the DMV. Direct PIC microinjection (0.232 nmol) into the DMV produced a pattern of responses similar to those observed with BIC (which were also abolished by vagotomy or by MUS microinjections into the DMV). The antrum and pylorus were also responsive to DMV microinjections of both GABA antagonists. Microinjections of BIC or PIC into the DMV produced increases in gastric circular muscle activity that occurred less frequently than LESP effects, but also were eliminated by vagotomy. The high (0.550 nmol) dose of BIC increased gastric motility significantly more often than the low dose of BIC (p < 0.05). In addition, BIC (0.550 nmol) microinjections into the DMV increased gastric secretory volume (from 0.6 +/- 0.2 to 6.0 +/- 2.5 ml/15 min; p < 0.01) and total titratible acid (from 34.4 +/- 8.9 to 86.0 +/- 19.1 mEq/15 min; p < 0.01), and decreased gastric pH (from 4.63 +/- 0.44 to 3.50 +/- 0.49; p < 0.05). Vagotomy also eliminated the gastric secretory effects of DMV BIC. Direct microinjections of MUS into the DMV also blocked BIC- or PIC-induced changes in gastric motility and/or gastric acid secretion. Isotonic saline microinjected into the DMV did not increase basal or decrease stimulated gastric esophageal motility or gastric secretion. These data indicate that LESP, gastric motility, and gastric secretion are influenced by a tonic DMV inhibition mediated by GABAA receptor stimulation of the DMV. Because disinhibition of these receptors clearly activates the upper gut, future work should focus on identifying the nuclei providing this synaptic input to the DMV that might be involved in the functional regulation of upper gut motor and secretory function.     

Cuffed endotracheal tubes: mucosal pressures and tracheal wall blood flow

Eighteen brands of cuffed endotracheal tubes, including those with the new low pressure cuffs, were evaluated and compared. Experiments were performed in vitro on excised dog tracheae to measure the mucosal pressure exerted by the inflated cuffs. Pressure was measured directly with a mechanical sensor. Latex cuffs exerted the highest mucosal pressures, whereas silicone cuffs exerted the lowest mucosal pressures. Polyvinyl chloride cuffs exerted intermediate levels of mucosal pressure. With each material, predistended cuffs exerted lower mucosal pressures than nonpredistended cuffs. A second set of experiments was performed in vivo to determine the effect of mucosal pressure on tracheal wall blood flow. These studies employed a thermistor technic. The data showed that, when inflated sufficiently to seal within the trachea, stiff cuffs reduced blood flow more than compliant cuffs. With all cuffs, blood flow was reduced more at the mucosa than at deeper regions of the tracheal wall.It was concluded that for clinical use, compliant cuffs are preferable to stiff cuffs because they should cause less ischemia.     

Computerized thermistor technique for indirect studies of esophageal blood flow

1. Intestinal atrophy contributes to the clinical difficulties of patients on parenteral nutrition. Systemic administration of epidermal growth factor reverses this effect, but there is concern over the clinical safety of intravenous administration of growth factors. We therefore investigated whether administration of luminal epidermal growth factor could reverse the atrophy induced in a rat model of parenteral nutrition when epidermal growth factor was given alone or in combination with soya bean trypsin inhibitor to reduce proteolytic digestion of the epidermal growth factor. 2. Infusion of soya bean trypsin inhibitor alone decreased intraluminal tryptic activity by about 90% but did not result in increased proliferation. Intragastric infusion of epidermal growth factor (72 micrograms/day per rat) caused a 26% increase in proliferation (determined by 2-h metaphase arrest) in the duodenum (P < 0.01) when compared with animals receiving 'control' intragastric infusion. However, intragastric epidermal growth factor had no effect on more distal regions of the bowel, probably reflecting rapid proteolysis of the epidermal growth factor by luminal proteases. In contrast, a trophic effect of luminal epidermal growth factor was seen in the duodenum (28% increase, P < 0.01) and jejunum (24% increase, P < 0.05) of animals which had received epidermal growth factor with soya bean trypsin inhibitor. This was probably due to the soya bean trypsin inhibitor decreasing the rate of degradation of epidermal growth factor by intestinal proteases, allowing biologically active epidermal growth factor to reach more distal portions of the bowel.(ABSTRACT TRUNCATED AT 250 WORDS)     

The cochlear blood flow: a comparison between the laser Doppler and the microsphere surface methods

Since the introduction in the early 1980s, of the laser Doppler (LD) method for measuring cochlear blood flow (CBF) it has been debated whether the measured changes reflect the total or regional blood flow and whether the method per se influences the CBF. In order to answer those questions, the effect of one vasodilating drug, sodium nitroprusside, was investigated after topical application on the round window membrane (RWM) with respect to its influence on CBF. Two different techniques, the microspheres surface method and the LD method, were used. Untreated animals and animals which received saline or nicotine acid on the RWM were used as controls. The effects on CBF and blood pressure (BP) were continuously registered with LD. When a maximal flow had stabilized, 6 x 10(6) microspheres were injected into the left side of the heart. After the microspheres had been distributed within the body, the animals were killed. Both cochleae were microdissected and the microspheres counted turn by turn in the lateral wall. The number of spheres in the two ears was compared and the difference was recorded as the increase caused by the drug. The percentage change in CBF measured using the LD was compared with that obtained by using the microsphere surface method (MSM). No change in CBF measured by the two techniques was registered in the untreated animals, or after saline or nicotinic acid, while sodium nitroprusside induced a substantial increase in CBF. The mean percentage change of CBF measured with the LD method was compared with the calculated mean percentage change of microspheres for all turns in the cochlea, and in the first turn. Student's t-test and the linear correlation coefficient were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastric emptying after gastric interposition for esophageal carcinoma: comparison between the anterior and posterior mediastinal approaches

BACKGROUND/AIMS: Close observation and evaluation of the function of the transposed stomach after esophagectomy is essential. The present study uses the sulfamethizole capsule meal test to evaluate differences in gastric emptying between the anterior and posterior mediastinal approaches in patients undergoing esophagectomy. METHODOLOGY: Thirty-eight patients who underwent the esophagectomy and esophagogastrostomy for esophageal cancer were randomly divided into 2 groups: Group 1: anterior mediastinal approach, and Group 2: posterior mediastinal approach. Gastric emptying was studied using the sulfamethizole capsule meal test. Patients received sulfamethizole food capsules, 65 g of bread, and 150 ml of water. Plasma sulfamethizole levels were determined by high performance liquid chromatography (HPLC). RESULTS: Gastric emptying in both groups was significantly accelerated compared to healthy volunteers. Gastric emptying did not differ significantly between groups 1 and 2. CONCLUSIONS: The present data show that the sulfamethizole capsule meal test is an effective means of evaluating the emptying of the transposed stomach. Furthermore, when the stomach is used as an esophageal substitute following esophagectomy, gastric emptying does not differ according to the access route.     

Benzodiazepine receptors in chronic cerebrovascular disease: comparison with blood flow and metabolism

The brain benzodiazepine (BZD) receptor distribution in patients with chronic cerebrovascular disease was assessed with 123I-iomazenil (IMZ) SPECT, and the findings were compared with the data for the cerebral blood flow (CBF) and cerebral metabolism. METHODS: We examined nine patients with chronic cerebrovascular diseases, six patients with cerebral infarction and three with moyamoya disease. Iodine-123-IMZ SPECT images were obtained for 15 min, 3 hr after the administration of 167 or 222 MBq 123I-IMZ. In seven patients, the CBF and oxygen metabolism were measured by the 50 steady-state method. In two patients, the CBF and glucose metabolism were measured by 99mTc-HMPAO SPECT and 18F-fluoro-2-deoxy-D-glucose-PET, respectively. The brain was initially classified into 18 regions, and abnormalities in the BZD receptor distribution, CBF and cerebral metabolism were visually evaluated. The count ratio of lesion-to-contralateral normal region (L-to-C ratio) was then used for comparison. RESULTS: In the core of the infarct, the 123I-IMZ uptake decreased (L-to-C ratios of the blood flow 0.42 +/- 0.26; metabolism 0.45 +/- 0.24; and 123I-IMZ uptake 0.46 +/- 0.14). In the peri-infarct region, the 123I-IMZ uptake slightly decreased (L-to-C ratios of 0.81, 0.82 and 0.89, respectively). In the region of misery perfusion, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.73, 1.07 and 1.02, respectively). In the remote deafferentiated areas in the ipsilateral cerebrum, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.76 +/- 0.10, 0.75 +/- 0.04 and 0.98 +/- 0.05, respectively). In the remote areas in the contralateral cerebellum, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.84 +/- 0.08, 0.85 +/- 0.04 and 0.94 +/- 0.05, respectively). CONCLUSION: The BZD receptor distribution, as measured by 123I-IMZ SPECT, is not considered to reflect neuronal function, but it may reflect neuronal cell viability. Iodine-123-IMZ SPECT may, therefore, hold promise as a potential probe for neuronal damage.     

Relationship between liver function and splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 2)

A case is reported of persistent primitive trigeminal artery associated with recurrent facial pain and noncomitant strabismus by partial ipsilateral oculomotor palsy. Transcranial Doppler disclosed indirectly persistent carotid-basilar anastomosis. CT and angiography allowed complete diagnosis excluding a posterior communicating artery aneurysm, a Tolosa-Hunt syndrome and an ophthalmoplegic migraine. Steroid therapy is recommended treatment. Surgery should be considered when symptoms are intractable to medical therapy.     

Measurement of pancreatic blood flow to prevent pancreatic juice leakage after pancreas-preserving total gastrectomy for gastric cancer

Disintegration apparatus according to P.Ph was adepted to measure the disintegration rate of tablets. The data obtained for 10 batches of aminophenazone tablets with different content of gelatine (2-20%) showed that there is a linear correlation between the area under non-disintegrated tablets mass curves (AUDC) and the area under release curves (AURC) described by equation: AUDC = bcr AURC - acr.     

Spectral pattern of neonatal cerebral blood flow velocity: comparison with spectra from blood pressure and heart rate

BACKGROUND: Extrafusal muscle fibers of human striated skeletal muscles are known to have a uniform innervation pattern. Motor endplates (MEP) of the "en plaque" type are located near the center of muscle fibers and distributed within the muscles in a narrow band. The aim of this study was to evaluate the innervation pattern of human facial muscles and compare it with that of skeletal muscles. METHODS: Ten facial muscles from 11 human cadavers were dissected, the nerve entrance points located, and the dimensions measured. All muscles were stained in toto for MEPs using Acetylcholinesterase (AChE) and examined under the microscope to determine their location. Single muscle fibers were teased to evaluate the stained MEPs. RESULTS: The length of the different facial muscles varied from 29 to 65 mm, which correlated to the length of the corresponding muscle fibers. MEP zones were found on the muscles in the immediate vicinity of the nerves' entrance points and located eccentrically. Numbers and locations varied from muscle to muscle. Three MEP zone distribution patterns were differentiated: numerous small MEP zones were evenly spread over the muscle, a predominant MEP zone and two to three small zones were spread at random, and two to four MEP zones of equal size were randomly scattered. One MEP of the "en plaque" type was found in 73.8% of the muscle fibers and two to five MEPs were found in 26.2%. The distances between the multiple MEPs on one muscle fiber varied from 10 to 500 microm. CONCLUSIONS: This study suggests that facial muscles differ from skeletal muscles regarding distribution and number of MEPs. The eccentric location of MEP zones and multiple MEPs suggests there is an independent mechanism of neural regulation in the facial muscle system.     

The relationship between regional blood flow and contractile function in normal, ischemic, and reperfused myocardium

We administered streptozotocin (STZ) and alloxan (AL) to the musk shrew (Suncus murinus, Insectivora) to determine the effective diabetogenic dose of the two toxins for this species. A single intraperitoneal (i.p.) injection of 75 mg/kgBW or the consecutive 5-day s injection of 25 mg/kgBW of STZ to non-fasted shrews, effectively (100%) induced hyperglycemia (> or = 300 mg/dl) with hypoinsulinaemia (< 30% of control level) in male shrews at 10 days after administration. Morphological studies showed cytological changes of B cells in the pancreatic islets of diabetic shrews. Hyperglycemic shrews induced by STZ were thus in IDDM (insulin dependent diabetes mellitus), and showed high susceptibility to the diabetogenic effect of STZ as compared with rodents. Shrews showed a sex difference in the diabetogenic susceptibility to STZ as do mice (male > female). They also showed a species specific resistance to the diabetogenic effect of AL. Of the eight shrews (with 8-hr fasting) that has been treated with a single injection of 200 mg/kgBW of AL, seven (88%) survived at least 10 days, showing no signs of hyperglycemia. All shrews died within 3 day s after injection of 250 or 300 mg/kgBW. These results indicated that the STZ-induced diabetic shrew is a unique animal model and may be useful for IDDM research. On the other hand, the musk shrew was highly resistant to the diabetogenic effects of AL.     

A comparison of three radionuclide techniques for measuring blood flow to rat extremities

A detailed comparison of three radionuclide techniques to estimate blood flow was done in the rat hind limb under reduced, normal and increased blood flow. The techniques compared were the washout of intra-arterial and intra-muscular Xenon-133 and the accumulation of radioactive microspheres in the reference organ technique. There was no significant difference between the three techniques at each of the three flow states. This confirmed that the simpler I.M. Xenon technique is a useful and accurate technique in estimating low blood flow rates in small animals. It was found that the skin puncture had to be sealed after the intra-muscular injection of Xenon to obtain valid results.     

Gastric mucosal blood flow response to stress in streptozotocin diabetic rats: regulatory role of nitric oxide

To investigate cytoprotection against mucosal injuries of the stomach in patients with diabetes, we investigated gastric mucosal blood flow (GMBF), its response to a burn stress, and the involvement of nitric oxide (NO) in streptozotocin (STZ) diabetic rats. GMBF was measured by laser-Doppler velocimetry (LDV) and by the hydrogen gas clearance technique (HGC). The steady-state GMBF of STZ rats decreased according to the duration of diabetes, and insulin treatment blocked this decrease. Burn stress caused a rapid decrease in the GMBF. Reduction of the GMBF and gastric mucosal leakage of Evans blue (EB) after the burn stress were greater in the STZ rats than in the controls, but insulin treatment completely blocked this increase in EB leakage in the STZ rats. There was a significant negative correlation between the percent GMBF 3 h after the burn stress and EB leakage at the same time point. In the controls and the insulin-treated STZ rats, N-nitro-L-arginine (L-NNA), an NO synthase inhibitor, enhanced the decrease in postburn GMBF and EB leakage, but was without effect in the STZ rats. These results suggest that NO may be involved in the regulation of GMBF, and that persistent hyperglycemia may impair this regulation. These findings suggest that patients with diabetes have reduced cytoprotection against a variety of gastric mucosal injuries.     

Intracellular calcium and blood pressure: comparison between primary hyperparathyroidism and essential hypertension

Intracellular calcium has been reported to be increased in essential hypertension, and thought to play a role in its genesis through facilitation of vascular smooth muscle contraction. Since hypertension is more prevalent in primary hyperparathyroidism, intracellular calcium may also be increased in this condition. To investigate whether the hyperparathyroid condition, i.e., hypercalcemia and increased PTH per se, could be associated with high intracellular calcium, we measured intracellular calcium in platelets with the Quin-2 AM fluorometric method in 11 normotensive patients with primary hyperparathyroidism, 15 patients with essential hypertension, and 18 normal controls, all matched for age and sex. We repeated the measurements in 9 of the hyperparathyroid patients after successful surgery. We found that intracellular calcium was higher in normotensive patients with primary hyperparathyroidism than in normal controls (198 +/- 24 vs 113 +/- 11 nM, p < 0.05), but lower than in patients with essential hypertension (198 +/- 24 vs 286 +/- 38 nM, p < 0.05). Successful removal of a parathyroid adenoma decreased intracellular calcium from 215 +/- 22 to 116 +/- 19 nM, (p < 0.01). In the patients with primary hyperparathyroidism, intracellular calcium was strongly correlated with the levels of PTH (r = 0.87, p < 0.01), but not with the total serum calcium levels (r = 0.04, NS). The decrease in intracellular calcium after parathyroidectomy was also strongly correlated with the decrease in PTH (r = 0.84, P < 0.01), but not with the decrease in total serum calcium (r = 0.16, NS). In the patients with essential hypertension, intracellular calcium correlated well with systolic (r = 0.69, p < 0.01), diastolic (r = 0.76, p < 0.01) and especially mean arterial pressure (r = 0.86, P < 0.01). There was no correlation between blood pressure and intracellular calcium in the patients with primary hyperparathyroidism. We conclude that normotensive patients with primary hyperparathyroidism, as well as patients with essential hypertension, can have increased concentrations of intracellular calcium in platelets. The correction of the hyperparathyroid condition normalizes intracellular calcium concentration. The close correlation between PTH and intracellular calcium suggests that PTH may act as a ionophore for calcium entry into cells. Whether the increased levels of intracellular calcium may reflect a pre-hypertensive condition in normotensive patients with primary hyperparathyroidism remains to be determined.     

Acute cardiac failure: the relation between coronary flow and cardiac function

To study the effects of acute coronary hypotension on the working dog heart in situ, both coronary arteries were cannulated and perfused with oxygenated blood at controlled pressures (40 to 120 mm Hg). At a perfusion pressure of 120 mm Hg, total coronary artery flow appeared to be sufficient (0.95+/-0.08 ml/min-g) to maintain normal cardiac performance for a 2.5-hour observation period. During incremental decreases in coronary perfusion pressure, significant linear correlations were found between coronary flow and cardiac index (r=0.84), left ventricular maximum dP/dt (r=0.83), stroke index (r=0.82), stroke work (r=0.83) and mean arterial pressure (r=0.62). During simulated shock conditions (systolic arterial pressure, less than 75 mm Hg), relative reductions in coronary flow (-60.9+/-4.0%) paralleled changes seen in cardiac function and persisted for 28+/-4 min.     

Orthostatic hypotension in organic dementia: relationship between blood pressure, cortical blood flow and symptoms

Basal cell and squamous cell carcinomas are the most common skin cancers, occurring mainly on sun-damaged skin of old persons. Basal cell carcinoma is a neoplasm of follicular germinative cells which may infiltrate and destroy adjacent tissues, but rarely metastasizes. Five clinico-pathologic types of basal cell carcinomas can be recognized, namely, nodulo-ulcerative, superficial, morpheiform, fibroepithelial, and infundibulo-cystic. Actinic keratosis and Bowen's disease are intrepidermal proliferation of atypical keratinocytes that eventually may progress to become over squamous cell carcinoma. Lesions arising in sites of chronic injury or scarring bear an higher risk of metastases. Keratoacanthoma is a rapidly evolving tumor of keratinocytes that resolves spontaneously. Keratoacanthoma might represent a self-healing type of squamous cell carcinoma.     

A comparison of multimodal therapy and surgery for esophageal adenocarcinoma

BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.