Endoscopic retrieval of a broken and migrated esophageal metal stent.

In patients with inoperable malignant tumors of the esophagus or cardia, self-expanding metal stents are increasingly used to improve dysphagia. Usually, they are not difficult to place and, as compared to conventional plastic stents, complications such as stent migration or perforation, seem to occur less frequently. This is a report on a young patient with metastatic adenocarcinoma of the cardia, who was treated with a self expanding metal stent after endoscopic dilatation of a tumor stenosis in the distal esophagus. Immediately after the procedure, he was able to eat and gained weight. Within 6 weeks and while on continuous infusion of 5-fluorouracil, the patient complained about recurrent severe dysphagia. Plain x-ray demonstrated a broken and migrated stent, the 2 parts of which were seen in the stomach and the duodenum. The stent could be extracted endoscopically without any complication, but the procedure was difficult and lasted 4 h, as the stent broke 2 more times during retrieval.

Human small bowel motor activity in response to liquid meals of different caloric value and different chemical composition.

Previous animal studies have shown that the nature and duration of postprandial motility in the small bowel depend both on the caloric load and the chemical composition of a meal. It is not clear whether this is also true for the human small bowel. Therefore we investigated the motor activity of the human small bowel in response to nutrient liquids of different caloric value and different chemical composition. Ten human volunteers underwent three separate, 24-hr ambulatory manometry studies. They drank water, a pure glucose solution, and Intralipid 10% in volumes of both 300 and 600 ml. The caloric value of the nutrient liquids was 330 and 660 kcal, respectively. Records were analyzed visually for the reappearance of phase III of the MMC after ingestion of a test liquid, and a validated computer program calculated the incidence and amplitude of contractions during the postprandial period. Neither duration of the postprandial interval nor the mean incidence or mean amplitude of contractions were different between the fat and the carbohydrate solutions, but phase III reappeared significantly later after ingestion of the nutrient liquids than after water (P = 0.0002). Duration of the postprandial interval also depended on the volume or the caloric load of a liquid meal (P = 0.0012). Mean incidence of contractions tended to be higher after ingestion of nutrient liquids than after water (P = 0.059). We conclude that in ambulant subjects, small bowel motor activity in response to chemically diverse liquid meals is remarkably uniform. This is true for the duration of the postprandial motor activity, as well as the incidence and amplitude of contractions during that period. The caloric value of a liquid meal, however, regulates the duration of the postprandial interval in the human small bowel.

Liver transplantation in a 29-year-old patient with gallbladder carcinoma complicating primary sclerosing cholangitis.

Patients with primary sclerosing cholangitis (PSC) are at increased risk for cholangiocarcinoma. This tumor usually is a fatal complication, median survival after diagnosis is less than six months. In an asymptomatic 29-year-old patient with long-standing PSC and ulcerative colitis, routine abdominal ultrasound demonstrated an irregular mass, 11 x 13 mm, in the gallbladder. Cholecystectomy was performed, and histological examination demonstrated a moderately differentiated adenocarcinoma with infiltration of all layers of the gallbladder and invasion of local lymphatic vessels. Extensive diagnostic work-up failed to consistently demonstrate metastatic disease, and the patient was offered a liver transplantation. 24 months after the operation, the patient feels well and there is no indication of tumor recurrence. In carefully selected patients with gallbladder carcinoma complicating PSC, liver transplantation may be a therapeutic option.

Value of an extended monoethylglycinexylidide formation test and other dynamic liver function tests in liver transplant donors.

Measuring monoethylglycinexylidide (MEGX) formation after intravenous administration of lidocaine in potential organ donors (MEGX test) has been advocated as a useful test to select donor livers for transplantation, but some groups have demonstrated a low test efficacy. We, therefore, investigated the value of an extended MEGX formation test and the value of other dynamic liver function tests, in selecting suitable human donor livers. In 51 human multi-organ donors, we measured elimination of galactose, indocyanine green, and lidocaine, as well as formation of MEGX, at 15, 30, and 60 min after administration of the test substances. In the early postoperative period, the function of the transplanted liver was then classified as good or poor, as defined by a prothrombin time above or below 65% by day 4 and fibrinogen concentration above or below 300 mg/dl by day 7. Donor characteristics and preservation modalities were very similar between the two groups. Galactose, indocyanine green, and lidocaine metabolism failed to predict good or poor graft function in the early postoperative period. MEGX serum concentrations, however, were significantly higher in the group of donors whose organs functioned well in the recipients, as compared with donors whose organs functioned poorly in the recipients. This was true for MEGX concentrations at 15 min (117+/-9 vs. 90+/-9 ng/ml; P=0.03), 30 min (108+/-8 vs. 86+/-8 ng/ml; P=0.04), and 60 min (100+/-6 vs. 73+/-5 ng/ml; P=0.006). Extending the MEGX formation test from 15 to 60 min improved test efficacy. Maximal MEGX concentration in 9 or up to 12 consecutive blood samples, drawn between 3 and 120 min after lidocaine infusion, was also significantly higher in donors whose organs functioned well, than in donors whose organs functioned poorly (129+/-10 vs. 101+/-10 ng/ml; P=0.03). Although the groups with good and poor organ function differed significantly with respect to their MEGX serum concentrations, and although efficacy of the MEGX test was improved by extending the test from 15 to 60 min, the overlap in individual MEGX serum concentrations was still so wide that it is virtually impossible to predict early graft function only on the basis of the MEGX test in the donor. Therefore, the MEGX test, although of potential scientific interest, does not predict early graft function with an accuracy necessary for clinical use.

Conventional and quantitative liver function tests after hepatic transplantation: a prospective long-term follow-up.

In long-term survivors of liver transplantation, hepatic function is obviously of vital importance. Therefore, we prospectively performed conventional and quantitative liver function tests in patients who had survived a first transplantation for at least 4 years. Compared to 6 months after transplantation, serum bilirubin concentration and gamma GT activity were significantly lower after 3, 4, and 5 years (bilirubin 1.2 +/- 0.2 mg/dl at 6 months vs 1.0 +/- 0.1, 1.0 +/- 0.2, and 0.8 +/- 0.1 mg/dl respectively; gamma GT 106 +/- 0 33 U/l at 6 months vs 56 +/- 17, 67 +/- 35, 39 +/- 10 U/l respectively). At these points in time, blood levels of cyclosporin A were also significantly lower. Other parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH, total protein, thromboplastin time, partial thromboplastin time) were unchanged over time. Serial quantitative liver function tests (indocyanine green half-life, galactose elimination capacity, lidocaine half-life, and MEGX formation) also remained stable. Thus, we conclude that hepatic function remains stable in long-term survivors of liver transplantation for at least several years.

Oesophageal acid and salivary secretion: is chewing gum a treatment option for gastro-oesophageal reflux?

The presence of acid in the oesophagus has been shown to stimulate salivary secretion, but the relevance of this oesophago-salivary reflex for acid clearance in physiological and pathological gastro-oesophageal reflux (GOR) is unknown. This study was designed to investigate the interrelation between oesophageal acid and both resting and stimulated salivary secretion. In 10 healthy volunteers, the acid clearance times after bolus infusion of 20 ml of 0.1 N hydrochloric acid were measured by means of ambulatory oesophageal pH monitoring. With a constant swallowing rate and resting salivary flow, the acid clearance time was significantly longer with dry as opposed to wet swallows (12.6 +/- 2.6 vs. 6.9 +/- 1.9 min; p = 0.01). When the salivary flow was doubled by chewing a gum base (26.0 +/- 3.4 vs. 13.2 +/- 2.0 ml/15 min; p = 0.005), the acid clearance time was markedly shortened (6.9 +/- 1.9 vs. 2.3 +/- 0.2 min; p = 0.02). As compared with water control, salivary flow, pH, and protein content were not affected by a bolus infusion of hydrochloric acid. This was true both for resting and gum-stimulated salivary secretion. Our study suggests that an oesophago-salivary reflex becomes effective only in prolonged episodes of GOR. This may explain why the water brash phenomenon is not regularly experienced by all reflux patients. Our study also suggests that chewing gum might be a non-pharmacological treatment option for some patients with symptomatic GOR.

Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity.

Silymarin can be extracted from the milk thistle, and silibinin is the main component of the plant extract. Possibly due to their antioxidant and membrane-stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. Thus liver, kidney, erythrocytes and platelets have been protected from the toxic effects of ethanol, carbon tetrachloride, cold ischemia and drugs, respectively. The effect of silibinin on endocrine and exocrine pancreas, however, has not been studied. We therefore investigated whether silibinin treatment attenuates cyclosporin A (CiA) toxicity on rat endocrine and exocrine pancreas. Groups of 15 male Wistar rats were treated for 8 days with CiA and/or silibinin. On day 9, endocrine and exocrine pancreatic functions were tested in vitro. At the end of the treatment period, blood glucose levels in vivo were significantly higher in rats treated with CiA while silibinin did not affect glucose levels. In vitro, insulin secretion was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with CiA both insulin and amylase secretion were reduced. Silibinin and CiA had an additive inhibitory effect on insulin secretion, but silibinin attenuated CiA-induced inhibition of amylase secretion. Despite CiA treatment, amylase secretion was in fact restored to normal with the highest dose of silibinin. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. This combination of effects could be useful in the treatment of non-insulin-dependent diabetes mellitus. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. As this inhibitory effect is probably unspecific, silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.

[Hemolytic anemia as cause of a marked bilirubin increase in primary biliary cirrhosis]. / Hämolytische Anämie als Ursache eines auffälligen Bilirubinanstieges bei primärer biliärer Zirrhose.

HISTORY AND CLINICAL FINDINGS: 16 years ago a now 53-year-old woman was found to have primary biliary cirrhosis. 5 years later, after bleeding from oesophageal varices, she had a portacaval shunt. For several years she had been taking ursodeoxycholic acid (750 mg daily). Because of steadily increasing jaundice over the past few years she presented for possible liver transplantation. INVESTIGATIONS: There was a discrepancy between the markedly raised serum bilirubin concentration (7.8 mg/dl) and the only slightly raised or normal activities of alkaline phosphatase (247 U/l) and gamma-GT (21 U/l). Further tests confirmed that the patients had not only PBC but also Coombs-negative haemolytic anaemia (haemoglobin 10.7 g/dl, reticulocyte count 122/1000, indirect bilirubin 6.4 mg/dl, haptoglobin not demonstrated, lactate dehydrogenase 316 U/l). She had splenomegaly despite the portacaval shunt. Blood smear revealed spherocytes, but hereditary spherocytosis was not confirmed. TREATMENT AND COURSE: A six-week interruption of taking ursodeoxycholic acid led, as expected, to a rise in the activities of serum alkaline phosphatase and gamma-GT, while haemolysis parameters were not affected. CONCLUSION: Serum bilirubin concentration is a decisive prognostic factor in the course of primary biliary cirrhosis and is therefore of particular relevance for the indication of liver transplantation. The reported case demonstrates the importance of considering other causes of hyperbilirubinaemia.

Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ).

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.

Rat pancreas after long-term treatment with the somatostatin analogue octreotide.

Somatostatin is a potent inhibitor of endocrine and exocrine pancreatic secretion. However, it is not clear whether it also inhibits pancreatic growth. Therefore we treated male Wistar rats with a somatostatin analogue, octreotide (12-192 micrograms/(kg body wt.day)), over a period of 14 days. In a dose-dependent manner, this potent and long-acting analogue caused a reduction in weight of the pancreas and a reduction in pancreatic content of protein, DNA, trypsin, chymotrypsin, amylase and lipase, as well as pancreatic content of insulin-, glucagon- and somatostatin-like immunoreactivities. When growth of rat pancreas was induced by oral administration of camostate (200 mg/(kg body wt. day) or by subcutaneous administration of cholecystokinin (2 x 10 micrograms/(kg body wt. day)) over a period of 14 days, octreotide (12-192 micrograms/(kg body wt.day)) had the same effects, but these were even more pronounced. We conclude that somatostatin is an important regulator of pancreatic growth.

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ.

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment. In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.

[Amebic liver abscess with hepatobronchial fistula]. / Amöbenabszess der Leber mit hepatobronchialer Fistel.

Four weeks after a holiday in Kenya a 57-year-old woman developed a fever up to 40 degrees C, right upper abdominal pain, icteric sclerae, nausea and vomiting. Laboratory tests revealed leukocytosis (24,400/microliters), markedly accelerated erythrocyte sedimentation rate (123 mm/h) and moderately increased activity of liver enzymes in serum. The liver was unremarkable on ultrasound. Four days after hospitalization the patient complained of dyspnoea and pleuritic pain. Ultrasound examination and computed tomography showed an abscess in the right lobe of the liver. Amoebic abscess of the liver being the most likely diagnosis, although the relevant serological tests were unremarkable and a titre increase occurred only later, treatment was started with metronidazole (four times 500 mg daily intravenously) and paromomycin (three times 10 mg/kg daily). Her condition significantly improved within a day. Two weeks later, however, she developed chest pain, dyspnoea and cough productive of large amounts of white-yellow sputum, even though antibiotic treatment was continuing. A transdiaphragmatic rupture of the abscess with formation of a hepatobronchial fistula proved to be the cause of these symptoms. The patient was treated surgically by drainage and suturing-over of the extensive diaphragmatic defect and after 2 weeks she was discharged symptom-free on a maintenance dose of diloxanide furoate (three times 500 mg/d orally).