Use of argatroban during multi-organ procurement: pharmacokinetics and sequelae in recipient of transplanted liver.

This report illustrates potential concerns regarding the administration of Argatroban (AGN), a small molecule, direct thrombin inhibitor, within the setting of multi-organ procurement (MOP). Herein, we outline the case of a large AGN bolus to the donor during MOP, and the passive transfer of a coagulopathy to the recipient of the transplanted liver. From this, we conclude that caution should be exercised when AGN is used in the setting of MOP.

Molecular Adsorbent Recirculating System Support Followed by Liver Transplantation for Multiorgan Failure From Heatstroke.

BACKGROUND: Exertional heatstroke is an extremely rare cause of fulminant hepatic failure. Maximal supportive care has failed to provide adequate survival in earlier studies. This is particularly true in cases accompanied by multiorgan failure. METHODS AND MATERIALS: Our prospectively collected transplant database was retrospectively reviewed to identify patients undergoing liver transplantation for heatstroke between January 1, 2012, and December 31, 2016. We report 3 consecutive cases of male patients with fulminant hepatic failure from exertional heatstroke. RESULTS: All patients developed multiorgan failure and required intubation, vasopressor support, and renal replacement therapy. All patients were listed urgently for liver transplantation and were supported with the molecular adsorbent recirculating system while awaiting transplantation. All patients underwent liver transplantation alone and are alive and well, with recovered renal function, normal liver allograft function, and no chronic sequelae of their multiorgan failure at more than one year. CONCLUSION: Extreme heatstroke leading to whole-body organ dysfunction and fulminant liver failure is a complex entity that may benefit from therapy using the Molecular Adsorbent Recirculating System while waiting for liver transplantation as a component of a multidisciplinary, multiorgan system approach.

Intraoperative Continuous Veno-Venous Hemofiltration Facilitates Surgery in Liver Transplant Patients With Acute Renal Failure.

INTRODUCTION: We have aggressively used continuous veno-venous hemofiltration (CVVH) on high model for end-stage liver disease (MELD) score liver transplant patients with acute kidney injury and hypothesized that the addition of intraoperative CVVH therapy would improve overall outcomes. METHODS: We performed a retrospective review of all adult, single organ, liver transplant recipients requiring preoperative renal replacement therapy between January 1, 2011 and June 1, 2013. Intraoperative and perioperative records and laboratory values were collected and used to create a database of these patients. Patients were grouped according to whether or not they underwent CVVH at the time of liver transplantation. RESULTS: Twenty-one patients with new-onset renal failure requiring preoperative renal replacement therapy received a liver transplant alone. Fourteen received intraoperative CVVH and 7 patients did not. The average MELD score was similar between groups (34 for intraoperative CVVH vs 35; P = .8). Preoperative sodium and potassium were higher for the group receiving intraoperative CVVH, but still fell within normal ranges. Preoperative lactate levels were higher in the group that received intraoperative CVVH (4.7 vs 2.0 mmol/L; P = .01). Intraoperative CVVH did not decrease intraoperative transfusion requirements or intensive care unit (ICU) and hospital lengths of stay. Differences in reoperative rates did not reach statistical significance. All patients were weaned off renal replacement therapy. One-year patient survival rate was 86% for intraoperative CVVH versus 71% without. CONCLUSION: The judicious use of intraoperative CVVH therapy may permit patients with increasing severity of illness to achieve outcomes comparable with less ill patients.

Physiological and pharmacological interventions in radionuclide imaging of the tubular gastrointestinal tract.

Radionuclide studies of the gastrointestinal tract (GI) are used to measure GI function and to detect anatomic lesions such as Meckel's diverticuli. A variety of physiological and pharmacological interventions have been applied to both types of studies to gain a better understanding of GI function and to improve detection of disease. This article will review interventions useful in imaging the tubular GI tract. Discussed are the measurement of GI motility and function by gastric emptying and imaging studies for GI bleeding including the Meckel's scan. Interventions involving the hepatobiliary system are covered elsewhere in this issue.

Gastric emptying in patients with bulimia nervosa and anorexia nervosa.

A dual radioisotope technique was used to measure gastric emptying of a mixed liquid and solid meal in 11 patients with bulimia nervosa, and was compared with 10 patients with anorexia nervosa and a sex-matched control population. The relationship of body weight and gastrointestinal symptoms to gastric emptying was also examined. Gastric emptying of solids in patients with bulimia nervosa was similar to that in controls (gastric T1/2 131 +/- 15 min vs 119 +/- 7 min; mean +/- SEM). In contrast, patients with anorexia nervosa had overall delayed emptying (182 +/- 31 min; p less than 0.05); six patients had normal emptying of the solid components of the meal and four had markedly delayed emptying. Gastric emptying of liquids was similar in the bulimics and controls (gastric T1/2 48 +/- 5 min and 49 +/- 4 min, respectively), whereas the anorexics tended to have prolonged gastric emptying (65 +/- 11 min, p = NS). There was no correlation between body weight, gastrointestinal symptoms, and gastric emptying in either group. These findings suggest that gastrointestinal symptoms are unreliable indicators of gastric emptying in patients with eating disorders, and that gastric emptying studies should be performed in such patients before treatment with prokinetic agents is considered.

Obesity and weight reduction do not influence gastric emptying and antral motility.

A dual radioisotope technique was used to measure gastric emptying of a mixed solid and liquid meal in 30 obese (> 125% of ideal body weight) subjects and 23 age- and sex-matched nonobese control subjects. Gastroduodenal motility studies were also performed on seven obese and 10 nonobese subjects to compare postprandial antral motility. In addition, eight obese subjects underwent gastric emptying studies before and after substantial weight reduction (mean 8.3%). Gastric emptying of both solids and liquids was similar in obese and nonobese subjects, and antral motility indices did not differ between the groups. Gastric emptying rates before and after substantial weight reduction were similar. We conclude that neither gastric emptying nor antral motility appear to be abnormal in morbidly obese subjects; neither does gastric emptying appear to be affected by substantial acute weight reduction.

Misrepresentation of academic accomplishments by applicants for gastroenterology fellowships.

OBJECTIVE: To determine whether two applicants who misrepresented their accomplishments in applications for gastroenterology fellowships reflected isolated incidents or whether misrepresentation was more wide-spread. DESIGN: Retrospective review of all 236 applications submitted for fellowship in a recent year for confirmation of research experience and cited publications. RESULTS: 138 applicants (58.5%) reported research experience during residency in a U.S. training program. Research activity could not be confirmed for 47 of 138 applicants (34.1%). Fifty-three applicants (22.4%) reported published articles, and 16 of these applicants (30.2%) misrepresented articles. Misrepresentation included citations of nonexistent articles in actual journals, articles in nonexistent journals, or articles noted as "in press." CONCLUSIONS: Misrepresentation on applications for gastroenterology fellowships was common. The following steps are recommended: 1) Fellowship programs should require that copies of all publications and letters of acceptance for manuscripts in press be submitted with fellowship applications; 2) applications should contain a statement to be signed by the applicant that the information provided is accurate; 3) persons writing letters of recommendation should verify the information being submitted by applicants; 4) medical students and residents should be taught that embellishment of curricula vitae constitutes misconduct; and 5) institutions and professional organizations should develop policies to deal with this problem.

Influence of gender and menopause on gastric emptying and motility.

The aims of this study were to determine (a) if there are differences in gastric emptying rates of a mixed liquid and solid meal between men and women, (b) if menopausal status affects gastric emptying, and (c) whether differences in solid emptying rates are associated with alterations in postprandial antral motility parameters. A dual-isotope technique was used to measure gastric emptying in 20 men, 18 premenopausal women, 14 postmenopausal women, and 8 postmenopausal women taking estrogen and progesterone hormone replacement. A multilumen perfusion catheter was used to measure antral motility in 6 men and 6 premenopausal women. Premenopausal women, postmenopausal women, and postmenopausal women taking oral estrogen and progesterone had slower gastric emptying of liquids than did men (p less than 0.025, less than 0.05, and less than 0.025, respectively). Both premenopausal women and postmenopausal women taking sex hormone replacement therapy had slower emptying of solids than did men (p less than 0.025 and less than 0.05) but, in contrast to liquids, postmenopausal women not on hormone replacement emptied solids at a rate similar to that of men. There were no differences in postprandial antral motility parameters between men and premenopausal women. These findings support the hypothesis that sex steroid hormones have variable inhibitory effects on gastric emptying of a mixed meal and this should be considered when studying gastric emptying in disorders that occur predominantly in premenopausal women.

Colonic and anorectal function in constipated patients with anorexia nervosa.

OBJECTIVES: Many patients with eating disorders complain of severe constipation. Previous studies have suggested that constipation in patients with anorexia nervosa may be associated with slow colonic transit. However, it is unclear whether a refeeding program will alter colonic transit in these patients. The aim of this study was to investigate colorectal function by measuring colonic transit and anorectal function in anorexic patients with constipation during treatment with a refeeding program. METHODS: We prospectively studied 13 female patients with anorexia nervosa who were admitted to an inpatient treatment unit and compared them to 20 previously studied, age-matched, healthy female control subjects. Patients underwent colonic transit studies using a radiopaque marker technique and anorectal manometry measuring anal sphincter function, rectal sensation, expulsion dynamics, and rectal compliance. Patients were studied both early (< 3 wk) and late (> 3 wk) in their admission. We restudied two patients who had slow colonic transit. All patients also underwent structured interviews. RESULTS: Four of six patients studied within the first 3 wk of their admission had slow colonic transit, defined as > 70 h (108.0 +/- 17.0 h, mean +/- SEM), on initial evaluation. In contrast, none of the seven patients studied later than 3 wk into their admission had slow colonic transit. Two of the four patients with slow transit were restudied later in their admission and were found to have normal transit times. Rectal sensation, internal anal sphincter relaxation threshold, rectal compliance, sphincter pressures, and expulsion pattern were normal in all subjects. CONCLUSIONS: Despite complaints of severe constipation, colonic transit is normal or returns to normal in the majority of patients with anorexia nervosa once they are consuming a balanced weight gain or weight maintenance diet for at least 3 wk.

Gastric emptying response to variable oral erythromycin dosing in diabetic gastroparesis.

Intravenous erythromycin has been shown to improve gastric emptying in diabetic gastroparesis. Oral erythromycin also accelerates gastric emptying, but to a lesser degree. To determine if this is a dose-dependent phenomenon, gastric emptying was measured in 10 insulin-requiring diabetic patients with gastroparesis after administration of either 250 mg or 1000 mg of erythromycin or placebo. The drugs were orally administered in a randomized, double-blind fashion 30 min prior to ingestion of a meal containing [99mTc]-sulfur colloid-labeled beef stew and [111In]DTPA-labeled orange juice. Anterior and posterior gastric images were recorded for 3 hr at 15-min intervals using an externally positioned gamma camera. The results demonstrated that both doses of oral erythromycin significantly improved solid-phase gastric emptying. The mean half-emptying time of solids was decreased from 151 +/- 40 min with placebo to 58 +/- 10 min and 40 +/- 9 min with 250 mg and 1000 mg of erythromycin, respectively. However, a dose-dependent relationship was not demonstrated with the two doses of erythromycin employed. These results suggest that for most patients with diabetic gastroparesis, a single 250-mg dose of erythromycin will significantly improve gastric emptying. It is possible that a dose-dependent relationship will be demonstrated with doses of erythromycin less than 250 mg.

Endoscopic balloon dilation for ulcer-induced gastric outlet obstruction.

OBJECTIVE: To determine the safety and efficacy of endoscopic balloon dilation for ulcer-induced gastric outlet strictures. METHODS: Review of the cumulative experience from two institutions involving 30 patients who underwent endoscopic balloon dilation for peptic ulcer-induced gastric outlet obstruction. Follow-up was by standardized interview at a mean of 15 months (range 4-28 months). RESULTS: Symptoms occurred for an average of 6 months before dilation and included weight loss, epigastric pain, nausea, vomiting, early satiety, bloating, and anorexia. Gastric outlet strictures had a median diameter of 6 mm (range, 0-10 mm). Ten (33%) patients had active ulcers. Six-millimeter to 18-mm (median 15-mm) balloons were inflated a median of 2 times (range 1-4 times) for a median of 60 s (range 30-180 s). Fifty-one procedures (1.7/patient) were performed; 20 (67%) patients had one treatment and 10 (33%) had multiple treatments. Twenty-four (80%) patients achieved sustained symptom relief, 17 of 20 having a single procedure and 7 of 10 required multiple sessions. Dilation failed in 4 (13%) patients with long duodenal strictures. Two (6.7%) patients dilated to 18 mm suffered perforation. Both recovered uneventfully after surgery. CONCLUSIONS: Endoscopic balloon dilation is safe and effective for most patients with ulcer-induced gastric outlet obstruction.

Intestinal neuromuscular function after preservation and transplantation.

While it is well known that prolonged preservation of the intestinal graft causes severe mucosal damage after transplantation, little is known about the effect on neuromuscular function. The entire small intestine of adult hound dogs was flushed and preserved with cold lactated Ringer's solution and autotransplanted either immediately (n = 6) or after 24 hr (n = 6). Animals undergoing sham operation (n = 4) were used as a control. Fasting motility and the response of the intestinal smooth muscle and enteric nerves to bethanechol (100 microg/kg/0.5 hr, iv) and cisapride (0.5 mg/kg, iv) were determined by a multiple strain gauge method on Postoperative Days 2,4,7,14,21, and 28. Compared to the control, immediately transplanted grafts and those preserved for 24 hr developed delayed reappearance of migrating myoelectric complexes (MMC), hypercontractile activity, and reduced response to bethanechol and cisapride administration. Animals in the preservation group developed more abnormal fasting motility after transplantation, but responses to bethanechol and cisapride stimulation were not markedly different from those of the immediate group. The reappearance of MMC occurred 3 weeks postoperatively in the preservation group compared to 2 days in the immediate group. The results of our study indicate that intestinal dysmotility is augmented in prolonged-preservation grafts compared to those with brief preservation. The dysmotility was transient and normalized 3 to 4 weeks after surgery. Preservation and reperfusion injury to the neuromuscular system of intestinal grafts are reversible and are attenuated by simple hypothermia.

Postcholecystectomy pain syndrome: pathophysiology of abdominal pain in sphincter of Oddi type III.

BACKGROUND & AIMS: Persistent abdominal pain occurs in many patients after cholecystectomy, some of whom are described as having sphincter of Oddi dysfunction (SOD). Pain in SOD type III is thought to be of biliary origin with little objective data, and treatment is often unsatisfactory. Chronic abdominal pain without a biological disease marker is similar to irritable bowel syndrome, in which many patients exhibit visceral hyperalgesia. This study tested the hypothesis that duodenal-specific visceral afferent sensitivity exists in patients with SOD type III. METHODS: Eleven patients with chronic abdominal pain after cholecystectomy and 10 controls underwent duodenal and rectal barostat studies to evaluate visceral pain perception measured with a visual analog scale. All subjects underwent psychological testing. RESULTS: Patients with SOD type III exhibited duodenal but not rectal hyperalgesia compared with controls. There were no differences in duodenal compliance between the groups. Duodenal distention reproduced symptoms in all but 1 patient. Patients showed high levels of somatization, depression, obsessive-compulsive behavior, and anxiety. CONCLUSIONS: Patients with SOD type III exhibited duodenal-specific visceral hyperalgesia, and duodenal distention reproduced symptoms in all but 1 patient. Abdominal pain in these patients may not originate exclusively from the biliary tree.

Pathology of human intestinal transplantation.

BACKGROUND & AIMS: Intestinal transplantation is a developing therapeutic option for patients with irreversible intestinal failure or short bowel syndrome. The aim of this study was to delineate the histopathology of human intestinal allografts and to define the features of intestinal rejection. METHODS: The histological features of 3015 endoscopic biopsy specimens and 23 allograft specimens from 62 intestinal recipients were analyzed retrospectively and correlated with clinical findings. RESULTS: Acute allograft rejection was characterized by a varying combination of crypt injury, mucosal infiltration primarily by mononuclear cells (including blastic lymphocytes), and increased crypt cell apoptosis (more than 2 per 10 crypts). It represented a patchy, often ileal-centered process that could progress to mucosal ulceration; later episodes (more than 100 days posttransplant) tended to show lesser cellular infiltration and greater apoptosis than earlier episodes. Correlation with clinical rejection was good (false-positive rate of 9%; false-negative rate of 26%). Two resected specimens showed obliterative arteriopathy indicative of chronic rejection. In other specimens, preservation injury, cytomegalovirus infection, post-transplant lymphoproliferative disorder, and nonspecific features of active or past mucosal injury could be recognized. CONCLUSIONS: Mucosal biopsy specimens are a useful means of monitoring intestinal allografts. Based on features validated by clinical correlation, acute rejection can be identified reliably and can be differentiated from the other pathological processes affecting the intestinal allograft.