[Treatment of a postoperative rectal stenosis with a self-expanding biodegradable polydioxanone stent]. / Behandlung einer postoperativen Rektumstenose mittels eines selbstexpandierenden resorbierbaren Polydioxanon-Stents.

Rectal stricture is a serious although infrequent complication of transanal endoscopic microsurgery (TEM). In some cases, these strictures may be refractory to treatment by endoscopic balloon dilatation. Biodegradable stents might improve the outcome by providing an extended period of dilatation. Moreover, these stents can remain in place without the need to remove them. In the presented case, a biodegradable polidioxanone stent originally developed to treat benign oesophageal stenoses was used to treat a patient suffering from rectal stricture following a TEM.

Measuring the effect of a study meal on portal concentrations of glucagon-like peptide 1 (GLP-1) in non diabetic and diabetic patients with liver cirrhosis: transjugular intrahepatic portosystemic stent shunt (TIPSS) as a new method for metabolic measurements.

BACKGROUND: Diabetes in liver cirrhosis is associated with a blunted insulin response, which might be explained by an impaired release of the incretin hormone glucagon-like peptide 1 (GLP-1) into the portal circulation. AIMS: To investigate basal and stimulated portal venous and peripheral GLP-1 concentrations in non-diabetic (ND) and diabetic (D) patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic stent shunt (TIPSS) implantation. PATIENTS AND METHODS: After elective TIPSS portalvenous and peripheral probes were drawn from 10 ND and 10 D patients with stable liver disease during an oral metabolic test and plasma glucose, immunoreactive GLP-1, insulin and C-peptide were measured. RESULTS: The study meal led to a significant rise in portal GLP-1 levels in ND and D. Basal and stimulated portal GLP-1 concentrations were not significantly different between ND and D. Peripheral GLP-1 did not differ significantly from portal venous levels. Insulin response in ND was more pronounced in the portal blood than in the periphery and was absent in D. CONCLUSION: TIPSS allows a direct evaluation of hormonal changes in the portal circulation during an oral metabolic tolerance test. A disturbed GLP-1 secretion does not play a role in blunting the insulin response observed in patients with hepatogenous diabetes.

ESPEN Guidelines on Enteral Nutrition: Liver disease.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in patients with liver disease (LD). It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for patients with chronic LD in whom undernutrition is very common. ONS improve nutritional status and survival in severely malnourished patients with alcoholic hepatitis. In patients with cirrhosis, TF improves nutritional status and liver function, reduces the rate of complications and prolongs survival. TF commenced early after liver transplantation can reduce complication rate and cost and is preferable to parenteral nutrition. In acute liver failure TF is feasible and used in the majority of patients.

Fasting hyperglucagonemia in patients with transjugular intrahepatic portosystemic shunts (TIPS).

BACKGROUND: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). METHODS: Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). RESULTS: Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. CONCLUSION: In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.

The effect of recombinant human GH replacement therapy on lipoprotein(a) and other lipid parameters in adults with acquired GH deficiency: results of a double-blind and placebo-controlled trial.

The effect of GH substitution on serum lipids and lipoproteins, and in particular lipoprotein(a) (Lp(a)), was investigated in 32 adults with postoperative (acquired) GH deficiency as part of a double-blind, placebo-controlled trial. Seventeen men and fifteen women, aged 18-59 years (mean 42 years) from two centres (Hannover and Göttingen) were randomly assigned to two groups. Group P (placebo) received placebo for the first 12 months and recombinant human GH (rhGH) for the following 12 months (open phase). Group V (verum) was treated with rhGH for two consecutive periods of 12 months each. The target dose of rhGH was 2 U/m2 per day, given subcutaneously daily at bedtime. Serum concentrations of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides were determined at 0, 12 and 24 months. In group V, Lp(a) increased significantly in the first as well as in the second year of treatment (P=0.02, 12 months versus baseline; P=0.016, 24 months versus 12 months). In contrast, Lp(a) levels remained unchanged in group P during the first 12 months (P=0.826 versus baseline), but increased significantly (P=0.002) during the second year, when all patients were administered GH. The increase in Lp(a) after 12 months of rhGH replacement therapy in all 32 patients was significant for Lp(a) baseline concentrations both above and below 20 mg/dl and was independent of the apolipoprotein(a) isoforms. Total and LDL-C decreased significantly after 1 year and triglycerides after 2 years in group V. A significant reduction was also observed in the TC/HDL-C and the LDL-C/HDL-C ratios. Our study shows an unfavorable effect of rhGH replacement therapy on Lp(a) levels, which is, however, counteracted by a favorable effect of rhGH on TC, LDL-C and the TC/LDL-C and LDL-C/HDL-C ratios.

Presentation of a kindred with familial medullary thyroid carcinoma and Cys611Phe mutation of the RET proto-oncogene demonstrating low grade malignancy.

OBJECTIVE: Both multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are caused by germline mutations of the RET proto-oncogene. A broad spectrum of malignancy within and between families has been described with no clear genotype-phenotype correlation due to a scarcity of available data of large kindreds. DESIGN: Here we present the only known family with a germline mutation of codon 611 TGC to TTC (exon 10) in the RET proto-oncogene leading to a replacement of cysteine by phenylalanine (Cys611Phe or C611F). RESULTS: Twenty family members of this large kindred are gene carriers (GCs) and seven (5-13 years old) are potential carriers but have yet to be analysed. The clinical course of medullary thyroid carcinoma (MTC) in this family is characterized by a very slow evolution and progression of the tumour with no MTC-related death to date. Of 11 patients (30-69 years old) having undergone thyroidectomy six were classified as pT1, four as pT2 and one as C-cell hyperplasia according to the TNM system of the International Union Against Cancer. Due to cervical and mediastinal lymph node metastasis one patient (44 years old) had to be operated on a second time. The seven non-operated GCs of the fourth and fifth generation (17-26 years old) are yearly monitored with pentagastrin stimulation tests; one non-operated GC (43 years old) has refused any further investigations. Screening for primary hyperparathyroidism and phaeochromocytoma was negative in all cases. CONCLUSION: We suggest from these experiences that the general advice for thyroidectomy in early childhood should be modified in certain families, depending on genotype.

Glucose metabolism and liver cirrhosis.

Chronic liver disease is characterized by numerous metabolic alterations, predominantly catabolic, resulting in the clinical picture of malnutrition and even cachexia in some patients. The following review focuses on disturbances of glucose metabolism and of hormonal interactions that could contribute to the clinical picture of malnutrition seen in chronic liver disease. Body composition is altered in a characteristic manner with an increase in fat mass and a significant loss of muscle tissue. Furthermore, defective glucose storage due to reduced insulin sensitivity predominantly of muscle tissue has been observed. The pathogenesis of insulin resistance leading to an impaired glucose tolerance or a manifest diabetes mellitus is as yet unknown. A receptor/postreceptor dysfunction probably exists in chronic liver disease that might be explained by the following factors: 1. Altered membrane lipid composition and increased levels of free fatty acids; 2. long-lasting hyperinsulinemia; 3. increased plasma levels of insulin counteracting hormones such as growth hormone, glucagon, catecholamines and possibly cytokines; 4. a lack of liver-derived humoral factors with insulin-like activity, i.e. insulin-like growth factors I and II.

TIPS implantation raises leptin levels in patients with liver cirrhosis.

Increased leptin levels in patients with liver cirrhosis are postulated to result in malnutrition and increased energy expenditure. Since cirrhotic patients show improved nutritional status after a transjugular intrahepatic portosystemic stent shunt (TIPS), it was the aim of this study to evaluate plasma leptin levels and their influence on nutritional status prior to and after the TIPS procedure. We evaluated plasma leptin levels, body mass index (BMI), Child-Pugh score and pertinent biochemical parameters in 31 patients (19 men and 12 women) with severe complications of liver cirrhosis (74% ethyltoxic men, 50% ethyltoxic in women), prior to and after TIPS. Nineteen cirrhotic patients without TIPS served as controls. In women ascitic-free BMI significantly increased (from 22.8 +/- 4.6 kg/m2 to 23.9 +/- 4.9; p = 0.004 three months after TIPS), whereas in men only a tendency toward higher values (26.1 +/- 4.7 vs. 26.7 +/- 4.4; p = 0.28) was found. Analysis of peripheral venous leptin concentrations before and three months after TIPS revealed a significant increase in women (11.9 +/- 8.8 ng/ml vs. 18.6 +/- 14.9; p = 0.009) and in men (7.7 +/- 6.2 ng/ml vs. 12.2 +/- 9.0; p = 0.005). In addition, the leptin-BMI ratio increase significantly in women and men three months after TIPS implantation (women 0.49 +/- 0.29 vs. 0.73 +/- 0.52; p = 0.017; men 0.28 +/- 0.22 vs. 0.43 +/- 0.28; p = 0.002). On the other hand, patients without TIPS implantation showed no significant alterations of BMI and peripheral venous leptin concentrations. After TIPS implantation in liver cirrhotic patients, leptin levels were increased and the nutritional status improved. Therefore, our analysis suggests that in patients with predominantly ethyltoxic liver cirrhosis, elevated leptin levels are not a major reason for poorer body composition.

Sleep disorders and portal-systemic encephalopathy following transjugular intrahepatic portosystemic stent shunt in patients with liver cirrhosis. Relation to plasma tryptophan.

Neuropsychiatric symptoms due to any type of dysfunction and/or portal-systemic shunting are summarized as hepatic encephalopathy (HE). HE in the presence of liver cirrhosis and/or portal-systemic shunting has been termed portal-systemic encephalopathy (PSE). PSE is most frequent among the HE syndromes and is almost exclusively seen in patients with advanced cirrhosis and portal hypertension. Portal-systemic shunting either spontaneous due to portal hypertension, following surgical portocaval anastomosis, or subsequent to transjugular intrahepatic portosystemic stent-shunt (TIPSS) is regarded as the primary causative condition for PSE, not hepatic dysfunction per se. PSE may be considered as a disorder of multiple neurotransmitter systems among which derangements of the serotonergic system have been documented most consistently. Incipient PSE is frequently paralleled by the occurrence of sleep disorders, however, their relation to PSE remains unclear. We observed a transient increase of sleep disorders post-TIPSS, which were only in part correlated to other symptoms of PSE. Among the biochemical parameters studied only an association between arterial ammonia levels and sleep disorders became apparent, whereas no significant relation was observed for peripheral tryptophan.

[Pathologic fundus changes in advanced liver cirrhosis. Reduction of symptoms after portosystemic shunt]. / Pathologische Fundusveränderungen bei fortgeschrittener Leberzirrhose. Reduzierung des Befundes nach Anlage eines portosystemischen Shunts.

BACKGROUND: In patients with advanced cirrhosis and portal hypertension a portosystemic shunting procedure is often necessary. This induces haemodynamic changes in the systemic circulation. The aim of this study was to find out whether there were changes in the retinal perfusion as well. METHODS AND PATIENTS: 17 patients with mainly ethyl-toxic cirrhosis (13 male, 4 female; mean age 54 years, range 34-72 years) underwent ophthalmologic examination before and 3 months after TIPS (transjugular intrahepatic portosystemic stent shunt). RESULTS: Before TIPS there were pathological findings in 11 patients: In five cases cotton-wool spots, in three cases discrete vessel abnormalities, in two cases small intraretinal haemorrhages and in one case papilloedema. In all cases these pathological findings were similar in both eyes. Three months after TIPS all these changes had completely disappeared or were at least considerably declining. CONCLUSIONS: The pathological findings in patients with advanced cirrhosis were interpreted as signs of reduced retinal perfusion. After a portosystemic shunting procedure signs of recovery were seen.

[Acute esophagus variceal hemorrhage and portal vein thrombosis as a complication of TIPSS. An unusual emergency indication for liver transplantation]. / Akute Oesophagusvaricenblutung und Pfortaderthrombose als Komplikation nach TIPSS. Eine ungewöhnliche Notfallindikation zur Lebertransplantation.

Acute oesophageal variceal bleeding is a severe complication of portal hypertension caused by liver cirrhosis. The mortality of the first bleeding runs up to 50%. Recurrent bleeding deteriorates the long-term prognosis. The therapy of first choice for acute oesophageal haemorrhage is endoscopic sclerotherapy. A new option to decompress portal hypertension for patients who continue to bleed despite sclerotherapy is TIPSS-implantation. We report on a patient suffering from recurrent oesophageal haemorrhage caused by portal hypertension due to postalcoholic liver cirrhosis, who developed a portal vein thrombosis after TIPSS-implantation. TIPSS-procedure permitted a bridging period for five months, until eventually a severe uncontrollable oesophageal haemorrhage occurred and emergency liver transplantation was needed. The patient was discharged after 6 weeks from the hospital in excellent condition.

[Recent aspects of palliative treatment of metastasized colorectal carcinoma]. / Neuere Aspekte in der palliativen Behandlung des metastasierten kolorektalen Karzinoms.

BACKGROUND: Despite a decrease in both the incidence of colorectal carcinoma and the mortality due to this disease, it is still the second most common cause of death in the Western world. Refined surgery and adjuvant chemotherapy have not been able to prevent the frequent recurrence of colorectal cancer, often in a nonresectable state. In this palliative situation, which may already occur during initial presentation, the following treatment is indicated: best supportive care and a differential and stepwise chemotherapy. Palliative chemotherapy retards the progression of cancer disease and improves survival (from 6-9 months to 15-18 months). Chemotherapy should already be started in asymptomatic patients, if cancer disease is progressive. CHEMOTHERAPY: 5-fluorouracil (5-FU) remains the key drug for palliative chemotherapy. Drug effects and side effects critically depend on the mode of application and on biomodulation (e.g. by folinic acid [leucovorin, LV]). Compared with the traditional bolus therapy of 5-FU/LV, we prefer infusional therapy for 24 hours because of its higher effectivity and fewer side effects. Further drugs that may be given in addition to or as an alternative to 5-FU, are sodium folinate, raltitrexed and oral fluoropyrimidines (so-called prodrugs, e.g., capecitabine and tegafur-uracil [UFT]). These drugs are still under clinical investigation. Capecitabine, in particular, appears to be a useful alternative for intravenous 5-FU therapy. When compared with the traditional 5-FU bolus therapy (Mayo regimen), capecitabine is at least equally effective, but has fewer side effects. Furthermore, it can be given orally. If treatment failure occurs under 5-FU, the application of oxaliplatin or irinotecan may be useful for second- and third-line therapy (partial remission rates of 10% or 13-15%). FIRST-LINE THERAPY: Four randomized Phase-III studies demonstrate the effectiveness of additional therapy with oxaliplatin and irinotecan in combination with 5-FU for first-line chemotherapy of colorectal cancer. Triple therapy improves remission rates, quality of life and (shown only for irinotecan/5-FU/LV) survival rate, but causes more side effects and costs.

VLDL apolipoprotein B determination in blood serum following precipitation of LDL with polyvinylsulphate.

A method is described for the determination of VLDL apolipoprotein B by radial immunodiffusion (RID) in serum supernatants following precipitation of LDL with polyvinylsulphate. The measurement of VLDL apolipoprotein B is based on the incubation of the polyvinylsulphate supernatant with triglyceride lipase (330 kU/l end concentration) for 12-24 hours at 37 degrees C. A good measure of agreement was found for the corresponding VLDL apolipoprotein B values measured by RID in the polyvinylsulphate supernatants (y) and VLDL apolipoprotein B values calculated as tetramethylurea-insoluble protein in the d less than 1.006 kg/l serum fraction (x) (r = 0.88, y = 0.96x + 0.004, n = 54). Within the tested range of 1.2 mmol/l to 6.7 mmol/l triglycerides, the concentration of apolipoprotein B measured in the polyvinylsulphate supernatant showed a linear relationship. Correlation analysis of VLDL apolipoprotein B values and serum triglycerides and VLDL cholesterol, respectively, showed a good correlation (r = 0.77 and r = 0.75, respectively, n = 54). In the determination of VLDL apolipoprotein B measured in polyvinylsulphate supernatant, a variation coefficient of 4.3% (means = 10.1 mmol/l, n = 20) was found in relation to the precision in the series, and a variation coefficient of 11.4% (means = 5.3 mmol/l, n = 15) in relation to day to day precision.

[Portal hypertension--pathophysiology and therapeutic approaches]. / Portale Hypertension--Pathophysiologie und Therapieansätze.

The following review article describes pathophysiological aspects of portal hypertension in its first part, especially the topographic variety of the vascular collateral system creating the danger of variceal bleeding. The second part discusses different forms of therapy including pharmaco- and sclerotherapy as well as operative and interventional procedures. Beta-blocker-therapy preferentially serves for the primary and secondary prevention of variceal bleeding. Sclerotherapy appears as the dominant therapeutic tool for the management of acute variceal bleeding. New chances of therapy include variceal banding and the implantation of a transjugular intrahepatic portosystemic stent-shunt (TIPSS). Operative procedure loose their significance more and more by the wide-spread use of sclerotherapy and the chance of a definite therapy of portal hypertension (liver transplantation) and the use of nonoperative interventional procedure (TIPSS or TIPS) which are still under clinical investigation.