Quality of life measurements do not support palliative pancreatic cancer treatments.

Although resection for pancreatic cancer is occasionally curative, its major value lies in restoring patients to a more normal life. The objective of this study was to evaluate the functional quality of life (QoL) of patients undergoing various treatments for pancreatic cancer using a nationwide, multi-institutional, non-referral patient population. From 822 pancreatic cancer patients treated from 1989 to 1995, and listed in the Department of Defense (DoD) hospital central computerized tumor registry, we selected 781 with evaluable survival information. Local tumor registrars had contacted patients at least yearly and prospectively compiled a QoL index using a self-reported Karnofsky performance status (KPS); values were obtained for patients alive in March of 1995 and/or 1996. Survival duration and KPS scores were then compared by stage and treatment using analysis of variance (F-test). Resection significantly increased KPS and mean survival time with stage I-II cancers and improved mean survival time, but not KPS, in patients with node positive (stage III) disease. The projected five-year survival rate after resection in stages I-II was 24% but zero for stage III. Patients receiving combined chemo- and radiation therapies, whether given as adjuvant or primary treatment, had significantly longer mean survival duration. However, KPS scores were not higher in treated patients. These data indicate that patients live longer and better lives after resection of localized pancreatic cancers, but QoL measurements do not support resection for pancreatic cancer involving lymph nodes. Unresected patients selected for combined chemo- and radiation therapy live longer, but not better, lives.

Cytoskeleton as a target for injury in damaged intestinal epithelium.

This report summarizes the findings of a series of studies undertaken to discern the role of the cytoskeleton in intestinal injury and defense. Two established cell lines were used for these studies. IEC-6 cells (a rat intestinal cell line) were incubated in Eagle's minimal essential medium with and without 16, 16 dimethyl prostaglandin E(2) (dmPGE(2); 2.6 microM) for 15 minutes and subsequently incubated in medium containing 10% ethanol (EtOH). The effects on cell viability and the actin cytoskeleton were then determined. Using a similar protocol, Caco-2 cells (a human colonic cell line) were employed to assess the microtubule cytoskeleton under these conditions. In both cell lines, EtOH extensively disrupted the cytoskeletal component being evaluated coincident with adversely affecting cell viability. Pretreatment with dmPGE(2) increased cell viability and abolished the disruptive effects on both the actin and microtubule cytoskeleton in cells exposed to EtOH. Prior incubation with cytochalasin D, an actin disruptive agent, prevented the protective capabilities of dmPGE(2) in IEC-6 cells challenged with EtOH. Phalloidin, an actin stabilizing agent, demonstrated similar effects to that of dmPGE(2) by stabilizing the actin cytoskeleton and preserving cellular viability in IEC-6 cells in response to EtOH. In Caco-2 cells, taxol, a microtubule stabilizing agent, mimicked the effects of dmPGE(2) by increasing cell viability in cells exposed to EtOH and enhancing microtubular integrity. In contrast, pretreatment with colchicine, an inhibitor of microtubule integrity, prevented the protective effects of dmPGE(2). These findings support the hypothesis that the cytoskeleton may be a major target for injury in damaged intestinal epithelium, and that the protective action of dmPGE(2) is orchestrated through preservation of this target.

Store-operated calcium influx in human gastric cells: role of endogenous prostaglandins.

BACKGROUND: Store-operated calcium influx (SOCI) appears to be a key component in regulating processes such as gene expression and cellular metabolism in nonexcitable cells. Our objective was to determine what effect, if any, prostaglandin inhibition had on SOCI in human gastric cells. METHODS: SOCI was induced in human gastric cells (AGS) with thapsigargin, a microsomal Ca++ adenosine triphosphatase inhibitor. Quantitation of SOCI was achieved by two different methods: sustained intracellular calcium elevation and manganese (Mn++) uptake. Endogenous prostaglandin E2 (PGE2) synthesis was measured by enzyme immunoassay. Three different nonsteroidal anti-inflammatory drugs (NSAIDs; indomethacin, ibuprofen, and aspirin) were used to minimize the nonspecific actions of any individual agent. RESULTS: SOCI in AGS cells was inhibited by the store-operated Ca+2 channel blocker lanthanum (La+3) but not the voltage-operated Ca+2 channel antagonists verapamil or nifedipine. Each of the three NSAIDs equally inhibited SOCI. The inhibition of SOCI induced by indomethacin was partially reversed by the addition of exogenous PGE2. Finally, AGS cells exposed to thapsigargin demonstrated significantly increased endogenous PGE2 release. CONCLUSIONS: These data suggest that NSAIDs inhibit (or endogenous prostaglandins modulate) SOCI in human gastric cells, at least in part. Because SOCI appears to be a critical mechanism involved in cell proliferation, this may provide one explanation of how NSAIDs inhibit (and endogenous prostaglandins enhance) gastric epithelial renewal and repair.

Perforated appendicitis in children: risk factors for the development of complications.

BACKGROUND: Many aspects of the management of perforated appendicitis in children remain controversial. The objective of this study was to define risk factors associated with the development of postoperative complications in children undergoing treatment for perforated appendicitis. METHODS: We reviewed all children (age < 16 years) who were treated for perforated appendicitis at Cardinal Glennon Children's Hospital between 1988 and 1997. Inclusion criteria included either gross or microscopic evidence of appendiceal perforation. RESULTS: Of 285 children with perforated appendicitis, 279 underwent immediate operative treatment. Mean patient age was 7.7 years and there were no deaths. Major postoperative complications included intra-abdominal abscess (n = 17), ileus (n = 7), mechanical intestinal obstruction (n = 6), and wound infection (n = 4). All children who had a postoperative abscess had more than 5 days of symptoms before operation. Within this subgroup, drain placement was associated with not only decreased postoperative abscess formation and but also shorter duration of fever and length of hospitalization. The incidence of mechanical obstruction or ileus was not increased and the rate of wound infection was actually lower after drainage. CONCLUSIONS: Drain placement appears to be helpful in children with late diagnosis but is of little benefit when the duration of symptoms is less than 5 days. Thus it is likely that drains are most useful in patients with well-established and localized abscess cavities.

Treatment of refractory chylothorax with externalized pleuroperitoneal shunts in children.

BACKGROUND: Traditional therapy for refractory chylothorax in the pediatric population has included pleurodesis and thoracic duct ligation. These procedures are associated with high morbidity and questionable success rates. METHODS: We retrospectively reviewed our experience with 15 patients who underwent treatment for chylous effusions using pleuroperitoneal shunts with exteriorized pump chambers. Mean patient age at time of shunt placement was 2.1 (0.1 to 11.5) years and the most common indication (7 of 15) was refractory chylothorax following surgical correction of congenital heart disease. Mean chylothorax duration before shunt placement was 76 (5 to 810) days and shunts were in place for an average of 104 (12 to 365) days. A total of 19 chylous effusions (pleural or pericardial) were treated with shunts. RESULTS: Nine of 11 right-sided chylothoraces, 5 of 6 left-sided chylothoraces, and 2 of 2 chylopericardia resolved with shunt therapy (84% total). Pleuroperitoneal shunting failed to clear the effusion in 3 children. There were six episodes of shunt malfunction that were repaired and two episodes of infection. Inguinal or umbilical hernia developed in 4 patients. CONCLUSIONS: Externalized pleuroperitoneal shunting is a safe, effective, and minimally invasive treatment for children with refractory chylous effusions.

Nonsteroidal anti-inflammatory drugs attenuate proliferation of colonic carcinoma cells by blocking epidermal growth factor-induced Ca++ mobilization.

Numerous studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal carcinogenesis. We have previously reported that NSAIDs, in human colonic carcinoma cells (Caco-2), attenuate epidermal growth factor (EGF)-induced cellular proliferation through a process independent of their inhibitory effects on prostaglandin synthesis. Furthermore, separate studies have also suggested that NSAIDs inhibit EGF-induced store-operated Ca++ influx. Thus we developed the hypothesis that NSAIDs may limit the activity of EGF by altering intracellular Ca++ ([Ca++]i) mobilization. Serum-deprived Caco-2 cells were employed for all experimentation. [Ca++]i was measured with Fluo-3 and extracellular Ca++ influx was monitored by quenching Fluo-3 fluorescence with Mn++. Proliferation was quantitated with two assays: cellular nucleic acid and total protein content. Caco-2 cells exposed to EGF demonstrated an initial increase in [Ca++]i which was blocked by neomycin, an inhibitor of IPsubscript 3 generation, and the phospholipase C inhibitor U73122 but not U73343 (inactive control). This was followed by sustained extracellular Ca++ influx, which was attenuated with calcium-free buffer (-Ca++), the store- operated Ca++ channel blocker lanthanum, indomethacin, ibuprofen, and aspirin. In subsequent studies, cells were treated with either serum-free media or EGF +/- the aforementioned inhibitors, and again serum starved. Cells exposed to EGF +/- the inactive phospholipase C inhibitor U73343 demonstrated a significant increase in nucleic acid and protein. However, proliferation induced by EGF was not observed when [Ca++]i elevation was prevented by blocking either internal Ca++ store release via phospholipase C/IPsubscript 3 or sustained Ca++ influx through store-operated Ca++ channels. Sustained [Ca++]i elevation, as induced by EGF, appears to be required for mitogenesis. These data support our premise that one mechanism whereby NSAIDs may attenuate colonic neoplasia is by blocking EGF-induced Ca++ mobilization.

Calcium accentuates injury induced by ethanol in human gastric cells.

The mechanism(s) whereby ethanol induces cellular injury remains poorly understood. Furthermore, the role of calcium in gastric mucosal injury under in vitro conditions is poorly defined. The major objectives of this study were to (1) define the temporal relationship between intracellular calcium accumulation induced by ethanol and cellular injury, (2) characterize the mechanism(s) whereby ethanol increases cellular calcium content, and (3) determine whether calcium removal would attenuate ethanol-induced cellular injury. Human gastric cells (AGS) were used for all experiments. Sustained intracellular calcium accumulation induced by ethanol, but not transient changes, preceded and directly correlated with cellular injury. Cells exposed to damaging concentrations of ethanol demonstrated an initial calcium surge that appeared to be a consequence of inositol 1,4,5-triphosphate (IP3) generation and subsequent internal store release followed by a sustained plateau resulting from extracellular calcium influx through store-operated calcium channels. Finally, both morphologic (cellular injury) and functional (clearance of bovine serum albumin) changes induced by ethanol were significantly attenuated when extracellular Ca(+&plus) influx was prevented, and further decreased when intracellular Ca(++) stores were depleted. These data indicate that calcium plays a significant role in cellular injury induced by ethanol.

Role of calcium homeostasis in gastric mucosal injury and protection.

Using a human gastric mucosal cell line, known as AGS cells, we determined the role that perturbations in intracellular Ca2+ concentration [Ca2+]i might play in cellular injury induced by various damaging agents. For deoxycholate (CD) and ethanol (EtOH) induced damage, a concentration related increase in [Ca2+]i was noted that preceded and closely paralleled the magnitude of injury. Thus, the higher the concentration of DC or EtOH, the more profound were the changes in [Ca2+]i and the resultant degree of cellular injury. Pretreatment with a low concentration of DC (50 microM; called a mild irritant) that was not damaging by itself attenuated injury induced by a damaging concentration (i.e. 250 microM) of DC, and appeared to elicit this protective action through mechanisms that resisted intracellular Ca2+ accumulation. Additional studies indicated that the mechanism of aspirin damage may be similar and that other protective agents such as prostaglandins and growth factors appear to mediate their protective properties through prevention of intracellular Ca2+ alterations. We propose that agents that prevent mucosal injury mediate this activity through a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation.

Outcome of the antegrade colonic enema procedure in children with chronic constipation.

BACKGROUND: Chronic constipation and fecal incontinence in children related to pelvic trauma, congenital anomalies, or malignancy will eventually lead to significant social and psychologic stress. Maximal medical treatment (daily enemas and laxatives) can also be difficult to maintain in many children. METHODS: At our children's hospital, 11 children with chronic constipation or fecal incontinence or both underwent the antegrade colonic enema (ACE) procedure. The operation involved constructing a conduit into the cecum using either the appendix (n = 8) or a "pseudo-appendix" created from a cecal flap (n = 3). We report our surgical results. RESULTS: Mean child age was 9.6 (5 to 18) years. With a mean follow-up of 14 (6 to 24) months, 10 of the children (91%) had significant improvement and 7 children (64%) are completely clean with no soiling and controlled bowel movements after irrigation. CONCLUSIONS: Regular colonic lavage after the ACE procedure allows children with chronic constipation and fecal incontinence to regain normal bowel habits and a markedly improved lifestyle. This procedure should be considered before colostomy in children and adults for the treatment of fecal incontinence from a variety of causes.

Acute ovarian torsion in children.

BACKGROUND: Acute ovarian torsion (OT) is an uncommon cause of abdominal pain in children and is frequently confused with other conditions. METHODS: We reviewed the records (1983 to 1999) of all children treated for acute OT at our children's hospital. RESULTS: Mean child age (n = 51) was 12.5 +/- 0.3 years. Children presented with either right-sided (n = 29) or left-sided (n = 22) pain. Diagnosis of OT was confirmed preoperatively by ultrasound (73%) or computed tomography (CT) scan (10%) while nine children (17%) with right-sided pain underwent surgery for presumed appendicitis. Despite a relatively short time from diagnosis to surgery, all 51 children required salpingooophorectomy. Contralateral biopsy was performed in 29% and 57% had an appendectomy. Younger children more commonly had either a mature cystic teratoma or torsion with no underlying abnormality as an etiology compared with OT in older children that was more likely to result from either a follicular or corpus luteal cyst. Pathologic examination of the contralateral ovary and appendix was normal in all children who underwent biopsy and appendectomy. CONCLUSION: Ultrasonography with color doppler is helpful for differentiating acute OT from appendicitis. Although the twisted ovary can rarely be salvaged, the etiology is usually benign. Preoperative serum markers and contralateral ovary biopsy may be unnecessary.

Early aggressive treatment for Merkel cell carcinoma improves outcome.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of dermal origin. Treatment recommendations are limited owing to a paucity of retrospective data and an absence of prospective data. The objective of this study was to determine current therapeutic trends and their impact upon outcome. METHODS: A retrospective study (1983 to 1996) was performed with patients from the Department of Defense and our University-affiliated hospitals. RESULTS: Thirty-five patients were evaluated with a mean follow-up of 31 months. Overall, 1- and 2-year survival rates were 80% and 50%, respectively. Patients undergoing wide local excision, prophylactic lymph node dissection, and adjuvant radiotherapy had significantly decreased locoregional and distant recurrence rates and improved survival when compared with their counterparts. Adjuvant chemotherapy did not diminish recurrence rates nor improve survival. Both locoregional and distant recurrence significantly decreased survival. CONCLUSIONS: These data suggest that early aggressive treatment for MCC improves both tumor control and survival, whereas the early use of chemotherapy does not improve outcome.

A state-wide evaluation of appendectomy in children.

BACKGROUND: Traditional management of appendicitis in children involves open appendectomy (OA), an operation that is relatively inexpensive and carries few risks and complications. However, little information is available regarding the use, cost, and complication of laparoscopic appendectomy (LA) in children. METHODS: Our initial aim was to determine if LA is frequently performed in children (<15 years). We then compared the surgical results of OA versus LA. In conjunction with the Missouri Department of Health, we evaluated 793 children treated for appendicitis throughout the state between January 1997 and June 1997. The authors were blinded to the patient, surgeon, and hospital; no children were excluded. RESULTS: LA was infrequently performed in children with advanced disease. Overall, children undergoing LA were older and had a shorter hospitalization but no difference in hospital charge. When separated by child age, LA was associated with a shorter length of stay in all groups (0 to 5, 6 to 10, and 11 to 15 years) but only children in the 6 to 10 year range had a lower hospital charge when compared with patients undergoing OA. CONCLUSIONS: LA is becoming a common surgical approach for older children with simple appendicitis. Furthermore, these data suggest that LA, independent of individual surgeon or medical center, is associated with a decreased length of hospitalization without a significant difference in hospital charge.

Early hypotension worsens neurological outcome in pediatric patients with moderately severe head trauma.

PURPOSE: The objective of this study was to determine the morbidity associated with hypotension in the resuscitative phase of pediatric head trauma. METHODS: A retrospective review (1990 to 1995) was performed at a level-1 pediatric trauma facility. Inclusion criteria included a Glasgow coma score (GCS) of 6 to 8 and absence of penetrating trauma or bleeding disorders. The GCS was assigned using a postresuscitation examination by a neurosurgeon. Hypotension was defined as a blood pressure reading of less than the fifth percentile for age that lasted longer than 5 minutes. Episodes were monitored from the onset of injury through the first 24 hours of hospitalization. Glasgow outcome scale (GOS) was assigned based on a 3-month follow-up evaluation. Analysis of variance (ANOVA) and contingency table analysis were performed on all groups, and a P value of less than .05 was taken to represent statistical significance. RESULTS: Seventy-two patients met inclusion criteria. They had a mean GCS of 7.2 and a mean age of 6 years; 97% survived. Early hypotension was associated with worse neurological outcome (GOS) and prolonged hospitalization. There was no significant correlation between GOS and age, gender, injury mechanism, associated injuries, or transport time. CONCLUSIONS: These data suggest that maintaining adequate blood pressure during the early resuscitation of pediatric blunt head trauma patients may improve neurological outcome.

Characteristics of pediatric cervical spine injuries.

PURPOSE: The objective of this study was to assess the mechanisms and patterns of injury and outcome in children with cervical (C) spine trauma. METHODS: We reviewed the National Pediatric Trauma Registry between April 1994 and March 1999 and identified (by ICD-9 criteria) all cases of blunt trauma victims with cervical fractures, dislocations, and spinal cord injuries without radiographic abnormality (SCIWORA). Data are shown as mean +/- SEM. RESULTS: During the 5-year period, the incidence of blunt C-spine injury was 1.6% (n = 408 of 24,740 total entries). Mean age was 10.5+/-0.3 (1 to 20) years, and 59% were boys. Leading mechanisms were motor vehicle accidents (n = 179; 44%), sports (n = 66; 16%), and pedestrian injuries (n = 57, 14%). Younger (< or =10 years) children more often sustained high (C1 to C4) vs low (C5 to C7) injuries (85% v 57%; P<.01) and also had a higher incidence of dislocations (31% v 20%; P<.01) and cord injuries (26% v 14%; P<.01), whereas older children had more C-spine fractures (66% v 43%; P<0.01). Mortality rates (overall, 17%) were higher in younger children (n = 180) when compared with older children (n = 228; 30% v 7%; P<.01). Overall, the majority of deaths (93%) were associated with brain injuries. No children with cervical dislocations had neurologic sequelae. The preponderance of children with fractures (83%) also were without neurologic injury, whereas those associated with SCIWORA usually were (80%) partial. Overall, complete cord lesions were infrequent (4%). CONCLUSIONS: These data, representing the largest series to date, confirm that blunt C-spine injuries in children are rare. Patterns of injury vary significantly according to child age. Major neurologic sequelae in survivors is uncommon, does not correlate well with cord level, and rarely is complete.

Prostatorectal fistula associated with tubular colorectal duplication.

Tubular colonic duplications are exceedingly rare. The authors present an unusual case of a boy with a persistent prostatorectal fistula resulting from a tubular colorectal duplication. The current case is unique for 2 reasons: (1) the presence of a fistula without any concomitant genitourinary anomalies and (2) the existence of a prostatorectal fistula.

The impact of intraoperative culture on treatment and outcome in children with perforated appendicitis.

BACKGROUND: Most protocols for the operative treatment of perforated appendicitis use a routine culture. Although isolated studies suggest that routine culture may not be necessary, these recommendations generally are not based on objective outcome data. METHODS: The authors reviewed the records of 308 children who underwent operative treatment for perforated appendicitis between 1988 and 1998 to determine if information gained from routine culture changes the management or improves outcome. Inclusion criteria included either gross or microscopic evidence of appendiceal perforation. RESULTS: Mean patient age was 7.5 years, 51% were boys, and there was no mortality. The majority of children (96%) underwent culture that was positive for either aerobes (21%), anaerobes (19%), or both (57%). Antibiotics were changed in only 16% of the patients in response to culture results. The use of empiric antibiotics, as compared with modified antibiotics, was associated with a lower incidence of infectious complication, shorter fever duration, and decreased length of hospitalization. We also investigated the relationship between culture isolates and antibiotic regimens with regard to outcome. The utilization of antibiotics suitable for the respective culture isolate or organism sensitivity was associated with an increased incidence of infectious complication and longer duration of both fever and length of hospitalization. Finally, the initial culture correlated poorly with subsequent intraabdominal culture (positive predictive value, 11%). CONCLUSION: These outcome data strongly suggest that the practice of obtaining routine cultures can be abandoned, and empiric broad spectrum antibiotic coverage directed at likely organisms is completely adequate for treatment of perforated appendicitis in children.

Minimally invasive anterior spinal exposure and release in children with scoliosis.

BACKGROUND: The early experience with thoracoscopy in children has involved the diagnosis and treatment of pleural and pulmonary diseases. Recent advances have allowed surgeons to perform more complex procedures through video-assisted thoracoscopic surgery (VATS), potentially decreasing the pain and pulmonary impairment associated with an open thoracotomy. The authors report their initial experience with thoracoscopic assisted anterior spinal exposure and release as part of the treatment for children with spinal deformities. METHODS: A retrospective chart review of five children who underwent VATS for anterior spinal surgery between June 1995 and January 1997 was performed. RESULTS: The ages of the patients ranged from 11 to 16 years with a mean of 13.4 years. All patients had an anterior spinal release with or without fusion and same-day posterior spinal fusion with instrumentation. VATS was successfully completed in all patients without major morbidity and no mortality. The average operative time for the anterior portion of the procedure was 305 minutes, and a mean of 7 disc levels were released. Mean length of chest tube drainage and hospitalization were 6.8 and 8.6 days, respectively. CONCLUSIONS: The objectives of anterior exposure for spinal surgery in children can safely and effectively be accomplished using minimally invasive surgery.

Gastrointestinal complications postthoracotomy and postvagotomy.

Postthoracotomy gastrointestinal complications, although relatively uncommon, can be associated with significant morbidity and mortality. It is necessary to identify patients who are at high risk for gastrointestinal complications during the preoperative evaluation. Appropriate stress ulcer prophylaxis should be provided to high-risk patients, and enteral feeds should be initiated as early in the postoperative course as possible. Postoperative hypotension and massive blood transfusions can be avoided with early reexploration in the case of postoperative hemorrhage. Finally, unexplained abdominal pain must not be ignored; a high index of suspicion should be maintained, with early and liberal use of diagnostic tools such as standard radiography, CT, endoscopy, and angiography. Consultation should be requested from a surgeon experienced in abdominal catastrophes. Early laparotomy with aggressive operative management can be lifesaving therapy but must be not applied in a cavalier fashion, as many of these disorders can and should be managed conservatively.

Adaptive cytoprotection induced by ethanol in human intestinal cells: role of prostaglandins and calcium homeostasis.

OBJECTIVE: To determine whether adaptive cytoprotection exists in human intestinal cells under in vitro conditions and what role, if any, endogenous prostaglandins or calcium may play in mediating this protective response. SUMMARY BACKGROUND DATA: Adaptive cytoprotection can be defined as that process whereby the administration of a low concentration of a damaging agent, termed a "mild irritant," which by itself is not injurious, can attenuate gastrointestinal mucosal injury subsequently induced by the application of higher concentrations of the same or other necrotizing agents. Despite substantial investigation, the mediator or mediators of adaptive cytoprotection remain poorly understood. METHODS: Postconfluent Caco-2 cells were used in all experiments. Cellular death was quantitated using a dual-component fluorescent assay. Changes in intracellular calcium concentration were quantitated by measuring fluorescent signal changes of the single wavelength calcium indicator (Fluo-3). Finally, prostaglandin E2 release into the media was quantitated by radioimmunoassay. RESULTS: Pretreatment of Caco-2 cells with low concentrations of ethanol (mild irritant) significantly attenuated injury induced by higher damaging concentrations of ethanol. The protection conferred by the mild irritant was directly dependent on both the concentration of the irritant used and the duration of exposure and was abrogated when cells were pretreated with an endogenous prostaglandin inhibitor (indomethacin) or if the mild irritant was administered in calcium-free media. Cells exposed to ethanol had a significant and concentration-dependent increase in intracellular calcium concentration, an effect that was highly related to cellular injury. Pretreatment with a mild irritant significantly decreased intracellular calcium increases induced by not only ethanol but also by a calcium ionophore (A23187). Cells treated with low concentrations of ethanol demonstrated no significant elevation in prostaglandin E2 release. CONCLUSIONS: Adaptive cytoprotection induced by ethanol exists in human colonocytes under in vitro conditions independent of mucosal blood flow, neural innervation, or circulating humoral factors. The authors' data suggest that this response does not require endogenous prostaglandin synthesis but may involve processes whereby intracellular calcium accumulation is prevented.