[Highlights in gastroenterology 2006].
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Adult↗
Biomedical subjects
B Müllhaupt
Publications and source records attributed to B Müllhaupt.
Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis.
The aim of this review was to assess the impact of transarterial chemoembolization (TACE) as a neoadjuvant therapy prior to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). An electronic search on the Medline database (1990-2005) was used to identify relevant articles. The studies were reviewed and ranked according to their quality of evidence using the grading system proposed by the Oxford Centre for Evidence-based Medicine. As a bridge to OLT, pretransplant TACE does not improve long-term survival (grade C). There is currently no convincing evidence that TACE allows to expand the current selection criteria for OLT, nor that TACE decreases dropout rates on the waiting list (grade C). However, TACE does not increase the risk for postoperative complications (grade C). There is insufficient evidence that TACE offers any benefit when used prior to OLT, neither for early nor for advanced HCC. Well-designed randomized controlled trials are needed to define the role of TACE in OLT patients.
Carcinoma, Hepatocellular↗
Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and up to moderate fibrosis.
Health regulatory approval of the 1.5 microg/kg body weight dose of pegylated interferon (PEG-I) alpha-2b in combination with ribavirin for the treatment of chronic hepatitis C was based on a study using PEG-I alpha-2b at doses of only 0.5 and 1.5 microg/kg body weight (BW), in spite of the previously shown flat dose-response curve at doses of > or =1.0 microg/kg. Our aim was to compare PEG-I alpha-2b 1.0 microg/kg with 1.5 microg/kg, both in combination with ribavirin. Open-label, randomized study in 227 patients with biopsy-proven chronic hepatitis C (Metavir < or =F2), receiving oral ribavirin (400 mg, twice daily) in combination with subcutaneous PEG-I alpha-2b (1.0 or 1.5 microg/kg, once weekly) for 24 weeks (genotype 2 or 3), or 48 weeks (other genotypes), followed by a 24-week drug-free period. Virologic response rates did not differ between the two doses of PEG-I alpha-2b: in patients infected with hepatitis C virus (HCV) genotype 1 or 4 treated with PEG-I 1.0 microg/kg BW, 38% (22/58) had a sustained virologic response compared with 39% (27/70) in the PEG-I 1.5 microg/kg BW dose group (P = ns). The corresponding values in patients infected with HCV genotype 2 or 3 were 71% (39/55) and 81% (29/36) respectively (P = ns). Adverse events led to transient or permanent dose reductions in fewer patients in the 1.0 microg/kg BW dose group (48/113 patients; 42%) than in the 1.5 microg/kg BW dose group (63/106 patients; 59%, P = 0.015). Furthermore, 89% of patients treated for 24 weeks but only 58% of patients treated for 48 weeks (P < 0.001) tolerated the treatment without relevant dose reduction or premature termination. In combination with ribavirin, PEG-I alpha-2b 1.0 microg/kg was as effective as 1.5 microg/kg but was better tolerated in patients with chronic hepatitis C and up to moderate fibrosis.
Adolescent↗
[Gastro-highlights 2004].
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Education, Medical, Continuing↗
[Highlights in gastroenterology 2004].
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Colonoscopy↗
Impact of etiology on the painful early stage of chronic pancreatitis: a long-term prospective study.
BACKGROUND AND AIM: This prospective study aimed to investigate the impact of etiology on the pain profile in relation to alterations of function and morphology from early to advanced chronic pancreatitis (CP). METHODS: Our mixed medico-surgical cohort comprised 265 patients with alcoholic (ACP), 21 with idiopathic "juvenile" (IJCP), 46 with idiopathic "senile" (ISCP) and 11 with hereditary CP (HPCP). The patients were followed regularly from onset of disease according to the protocol published previously. RESULTS: Males predominated in ACP, IJCP, ISCP (> 71%) but not in HP (46%). Age at onset (median) was 10, 23, 36 and 62 years in HP, IJCP, ACP and ISCP, respectively. Follow-up from disease onset ranged from 14 to 36 years. The progression to late-stage CP, documented by exocrine insufficiency (86-100%) and calcification (80-91%) lasted 2 to 5-fold longer in HP/IJCP compared to ACP. Early stage CP, characterized by recurrent pancreatitis prevailed in > or = 90% of patients, except for those with ISCP (48%), and lasted up to 5-fold longer in HP/IJCP compared to ACP. Surgery for severe pain was required for ACP/IJCP in 57% of the patients compared to < 27% in HP/ISCP. Permanent pain relief regularly occurred in late-stage CP irrespective of etiology and surgery. CONCLUSION: The clinical profile of the 4 "etiological" subgroups is predictably different in the painful early (precalcific) CP stage.
Adolescent↗
Cigarette smoking accelerates progression of alcoholic chronic pancreatitis.
BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes. AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes. PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries. METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption. RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis. CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.
Adult↗
[Differential diagnosis of jaundice].
Jaundice, a common condition with many different causes, is marked by yellow discoloration of the sclerae, mucous membranes and skin. Apart from a careful history and clinical examination, the determination of the liver enzymes is the most important step to unravel the underlying etiology. The most common etiology for an isolated hyperbilirubinemia with normal liver values is Gilbert's disease. If the liver enzymes are abnormal, the relationship between transaminases and cholestatic enzymes allows to distinguish between a hepatocellular and cholestatic dysfunction and to guide the further diagnostic and therapeutic modalities accordingly.
Algorithms↗
[Diarrhea].
Diarrhea is not a single disease, but only a symptom of different diseases. Diarrhea is characterized by an increase in bowel movements (more than three per day) and an increased liquidity of stools. Acute diarrheas are defined as those that last less than four weeks, whereas chronic diarrheas persist for more than four weeks. The pathophysiological basis of diarrhea is a disturbed enteral water- and electrolyte balance, which can be caused by an increased secretion of osmotically active electrolytes (secretory diarrhea) or the increased ingestion of osmotically active substances (osmotic diarrhea). The stool characteristics allows to distinguish watery, bloody and fatty diarrhea. Acute diarrheas are mostly caused by an infectious agent (viruses, bacteria and parasites), whereas the differential diagnosis of chronic diarrhea is considerably larger and therefore the diagnostic work-up is more complex.
Acute Disease↗
[Acute fatty liver in pregnancy: clinical and histopathological course. Case report].
Acute fatty liver of pregnancy is a rare disease which may be letal if diagnosis is missed. The pathogenesis is not completely clear, but there is some evidence that some cases have been associated with a genetic deficiency of fatty acid beta-oxidation. Other predisposing factors include primiparity, multiple pregnancy, male fetal sex and pre-eclampsia. Clinical presentation and laboratory findings are often unspecific. Increasing serum aminotransferases are characteristic in the early stage of the disease. Liver biopsy establishes the diagnosis and typically shows microvesicular, centrilobular fatty changes of hepatocytes. Differential diagnosis includes the HELLP-Syndrome, cholestasis of pregnancy, pre-eclampsia and viral or drug induced hepatitis. Without adequate treatment liver failure with coagulopathy and encephalopathy may develop. Two cases of acute fatty liver in pregnancy in an early stage are presented. Clinical and histopathological findings as well as diagnostic and therapeutic procedures are discussed.
Adult↗
[Expandable esophageal stent for the treatment of esophageal fistula].
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Adult↗
Is the diagnostic yield of upper GI endoscopy improved by the use of explicit panel-based appropriateness criteria?
BACKGROUND: Increasing the appropriateness of use of upper gastrointestinal (GI) endoscopy is important to improve quality of care while at the same time containing costs. This study explored whether detailed explicit appropriateness criteria significantly improve the diagnostic yield of upper GI endoscopy. METHODS: Consecutive patients referred for upper GI endoscopy at 6 centers (1 university hospital, 2 district hospitals, 3 gastroenterology practices) were prospectively included over a 6-month period. After controlling for disease presentation and patient characteristics, the relationship between the appropriateness of upper GI endoscopy, as assessed by explicit Swiss criteria developed by the RAND/UCLA panel method, and the presence of relevant endoscopic lesions was analyzed. RESULTS: A total of 2088 patients (60% outpatients, 57% men) were included. Analysis was restricted to the 1681 patients referred for diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit criteria. No cancer was found in upper GI endoscopies judged to be inappropriate. Upper GI endoscopies judged appropriate or uncertain yielded significantly more relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio 2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper GI endoscopy was significantly influenced by appropriateness, patient gender and age, treatment setting, and symptoms. CONCLUSIONS: Upper GI endoscopies performed for appropriate indications resulted in detecting significantly more clinically relevant lesions than did those performed for inappropriate indications. In addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged to be inappropriate. The use of such criteria improves patient selection for upper GI endoscopy and can thus contribute to efforts aimed at enhancing the quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).
Adult↗
[Therapy of chronic hepatitis B and C].
10% of patients infected with the hepatitis B virus develop a chronic hepatitis. The only approved therapy is interferon-alpha, which leads in 30-40% to a HbeAg/anti-Hbe Seroconversion. In contrast, the infection with the hepatitis C virus leads to a chronic hepatitis in over 80%. Here again interferon-alpha is the only approved drug to treat these patients. A sustained normalisation of transaminases and a sustained virological response can be achieved in 20 to 40% at most. In view of these unsatisfactory treatment results, new treatment options are currently being evaluated for both infections. Treatment with nucleoside analogues are being tested in patients with chronic hepatitis B and for the treatment of chronic hepatitis C a combination treatment seems most promising.
Antiviral Agents↗
5'-Cytosine DNA-methyltransferase mRNA levels in hereditary colon carcinoma.
DNA methylation plays an important part in the regulation of gene expression. Alterations in DNA methylation in tumours have been reported and have been used to generate hypotheses about mutagenesis and silencing of tumour suppressor genes. However, the underlying mechanism is still poorly understood, and conflicting data on the levels of overexpression of 5'-cytosine DNA methyltransferase in sporadic colon carcinoma have been published. We used a competitive RT-PCR assay for quantification of mRNA of 5'-cytosine DNA methyltransferase in colon biopsies obtained from patients with hereditary colon carcinoma syndromes and compared the results with those obtained in a control group. No significant difference was found between the flat mucosa of FAP patients and the mucosa of the control group. In FAP and HNPCC patients, the 5'-cytosine DNA methyltransferase mRNA levels of adenomas were significantly higher (P<0.05) than of flat mucosa in the same group, but both showed great variability from patient to patient. Our findings suggest that the mRNA levels of methyltransferase cannot be used as predictive marker for screening in families affected by hereditary colon carcinoma.
Adenomatous Polyposis Coli↗
Phenotypic differences in familial adenomatous polyposis based on APC gene mutation status.
BACKGROUND: Familial adenomatous polyposis (FAP) is a clinically well defined hereditary disease caused by germline mutations within the adenomatous polyposis coli (APC) gene. Although several techniques are applied in the mutation analysis of FAP kindreds about 20-50% of cases remain unclear, with no APC mutation identified (APC negative). AIMS: To delineate phenotypic differences between APC positive and APC negative patients with respect to colonic and extracolonic disease in order to determine whether additional mechanisms are involved in the pathogenesis of FAP. METHODS: The entire coding region of the APC gene was analysed using single stranded conformation polymorphism and protein truncation tests in 50 Swiss FAP families with a total of 161 affected individuals. Differences in phenotypic manifestation were statistically evaluated by Student's t test, Fisher's exact test, and chi2 test. RESULTS: Thirty six families (72%) were APC positive. Statistically significant differences between APC positive and APC negative groups were found for the mean age at diagnosis of colonic polyposis (35.2 versus 45.3 years, respectively) and for the occurrence of stomach polyps (14 patients, all APC positive). Additionally, APC negative patients displayed lower polyp numbers at diagnosis and less extracolonic manifestations. CONCLUSIONS: FAP kindreds without detected APC gene mutations present with a notably milder disease phenotype compared with APC positive families, suggesting that different genetic factors might be involved.
Adenomatous Polyposis Coli↗
[Steroid therapy and course of blood sedimentation rate in de Quervain's thyroiditis].
This study presents a retrospective analysis of clinical and laboratory results of 22 patients--predominantly younger women--with thyroiditis de Quervain. Diagnosis is based on clear leading symptoms like swelling and tenderness of the thyroid on pressure, swallowing with pain radiating to mandible and/or ears, fever and increased erythrocyte sedimentation rate (ESR). Half of the patients had slight anemia, leucocytosis without shift to the left, lymphopenia and thrombocytosis. The therapy of choice was prednisone, starting with an initial dose of usually 50 mg, reduced stepwise over 3 months under control of the clinical picture and the sedimentation rate. In a third of the patients clinical symptoms of the disease that had disappeared transiently redeveloped under reduction of prednisone without increase of the erythrocyte sedimentation rate. Raising the dose of prednisone for a short while led to prompt disappearance of symptoms. The ESR thus supports diagnostic investigations; however, it fails as a control parameter for the course of disease under treatment.
Adult↗
[Work analysis of residents in the medical outpatient clinic of the Zurich University Hospital].
Modern medical practice has led to progressive use of time-intensive, highly technical diagnostic and therapeutic measures. Meanwhile, the long working hours of hospital residents are reduced stepwise. In order to preserve adequate patient care, daily routine will have to be economized. We evaluated the present state of daily routine of residents at the outpatient clinic of the department of internal medicine, University Hospital, Zurich. Patient care consisted of roughly half the daily work, administrative matters occupied one third, and one sixth consisted of staff meetings, postgraduate teaching and other work. The main target optimization lies in the administrative area. Residents could be trained in more efficient time systems. Of particular interest would be the establishment of small strategic units adapting to their current use in private enterprise.
Education, Medical↗
The common pattern of cytokeratin alteration in alcoholic and cholestatic liver disease is different from that of hepatitic liver damage. A study with the panepithelial monoclonal antibody lu-5.
The patterns of cytokeratin as determined by murine monoclonal antikeratin antibody lu-5 (mAb lu-5) were quantitated in paraffin-embedded liver tissue from normal and diseased subjects. In tissue from healthy medical students, mAb lu-5 was found to decorate 2-4 periportal and 2-3 perivenular cell layers. Alcoholic liver disease was accompanied by a marked increase in intensity of mAb lu-5 antigen expression in zone I and III hepatocytes. Moreover, additional liver cells of both zones were progressively recruited, so that in advanced lesions all three lobular zones became positive. In mechanical as well as in drug-induced cholestasis, a similar increase of mAb lu-5 antigen expression was already observed in earlier stages of disease, including an earlier recruitment of zone II hepatocytes. In both alcoholic and cholestatic biopsies the intensity and extent of mAb lu-5 epitope expression increased with the duration and severity of disease. In primary biliary cirrhosis (PBC) and seemingly also in primary sclerosing cholangitis the increase and extent was more marked in zone I, the zone of assumed cholate accumulation. Changes in zone III, the territory of histologic cholestasis (bilirubinostasis), became evident only in late stages of PBC. Mallory bodies of alcoholic and cholestatic liver disease showed an identical mAB lu-5 antigen expression, thus giving rise to four different staining patterns. Changes of cytokeratin expression are similar in alcoholic and cholestatic liver diseases. In chronic viral hepatitis, however, cytokeratin alterations are discrete and restricted to precirrhotic/cirrhotic stages.
Antibodies, Monoclonal↗