Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt

BACKGROUND: In patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), prognostic scores may identify those with a poor prognosis or even those with a clear survival benefit. The Child-Pugh score (CPS) is well established but several drawbacks have led to development of the model of end stage liver disease (MELD). AIM: The aim of the study was to compare the predictive power of CPS and MELD, to validate the original MELD formula, and to assess the predictive value of the determinants used in the two prognostic scores outside of a study setting. PATIENTS: A total of 501 patients underwent elective TIPS placement and 475 patients fulfilled the inclusion criteria. METHODS: Data of all patients undergoing elective TIPS in one university hospital and four community hospitals in Vienna, Austria, between 1991 and 2001, were analysed retrospectively. The main statistical tests were Cox proportional hazards regression model, the log rank test, Kaplan-Meier analysis, and concordance c statistics. RESULTS: Median follow up was 5.2 years and median survival was 4.6 years. During follow up, 230 patients died, 75 within three months after TIPS placement. In stepwise proportional hazards analyses, independent predictors of death were creatinine level, bilirubin level, age, and refractory ascites. MELD was better in predicting survival in a stepwise Cox model but both scores were equally predictive in c statistics for one month, three month, and one year survival. Renal function was the strongest independent predictor of survival. CONCLUSIONS: Although MELD was the primary predictor of overall survival in multivariate analysis, c statistics showed that both scores can be used for patients undergoing TIPS with equal accuracy. For assessing prognosis in patients undergoing TIPS implantation, there seems little reason to replace the well established Child-Pugh score.     

Differential diagnosis of benign and malign pancreatic masses with 18F-fluordeoxyglucose-positron emission tomography recorded with a dual-head coincidence gamma camera

INTRODUCTION: Metabolic imaging using 18F-fluordeoxyglucose and a ring-positron emission tomography camera is an established method in the differential diagnosis of pancreatic masses. Ring-positron emission tomography cameras, however, are expensive and available in only few specialized centres. The aim of this study was to investigate how far 18F-fluordeoxyglucose scan with a conventional dual-head gamma-camera could differentiate between benign and malign pancreatic masses. MATERIAL AND METHODS: Forty-one patients (male/female: 25/16; mean age: 64.0 years; range: 41-86 years) with a pancreatic mass detected by ultrasound, computed tomography or MRI were included. In all patients 18F-fluordeoxyglucose scan was performed after overnight fasting and injection of 4 mCi 18F-fluordeoxyglucose using an ADAC Vertex MCD dual head gamma-camera (ADAC; Milpitas, California, USA), equipped with a 5/8-inch NaI-crystal. Images were acquired through a 180 degrees grade rotation in the three dimensional mode. The chosen matrix was 128 x 128 x 16, a Butterworthfilter (ADAC) was used and data were transferred into visible sinograms via Fourier-Rebinning. Coronar, sagittal and transversal slices of 3.9 mm thickness each were acquired. Focal tracer enhancement was suspicious for a malignoma and therefore regarded as positive, diffuse or no tracer uptake was suspicious for a benign process and was regarded as negative for cancer. DEFINITION OF GOLD STANDARDS: A diagnosis of cancer had to be confirmed histologically by specimens obtained by 18G-needle biopsy, surgical resection or at autopsy. A diagnosis of an inflammatory mass was considered proven, if no carcinoma could be found histologically in the surgically resected mass or at autopsy, or if there was no progression of the disease during a follow-up of at least 12 months. RESULTS: In 22 patients carcinoma was diagnosed (pancreatic cancer: n=17; endocrine tumour: n=3; carcinoma of the common bile duct: n=2). 18F-fluordeoxyglucose scan showed a focal tracer enhancement in 19 of these 22 patients (sensitivity: 86.4%). False negative results were acquired in two patients with cancer of the common bile duct and in one patient with poorly controlled insulin-dependent diabetes mellitus. In 19 patients the final diagnosis was an inflammatory pancreatic mass. 18F-fluordeoxyglucose scan showed a diffuse tracer enhancement in 15 of these 19 patients (specificity: 78.9%). False positive results were acquired in three patients whose blood tests showed signs of an acute episode of chronic pancreatitis. Positive and negative predictive values of 18F-fluordeoxyglucose scan were 82.6% and 83.3%, respectively. CONCLUSION: 18F-fluordeoxyglucose scan with a conventional dual-head gamma-camera is a highly sensitive and specific method in the differential diagnosis of benign and malign pancreatic masses.     

Very early viral kinetics on interferon treatment in chronic hepatitis C virus genotype 4 infection

BACKGROUND: Interferon (IFN)-resistant hepatitis C virus strains limit efficacy of antiviral combination therapy in patients infected with genotypes 1 and 4. A single test dose of IFN was useful to identify non-responders to IFN-alpha2b/ribavirin (RBV) or likely non-responders to pegylated (PEG)-IFN-alpha2a/RBV therapy in genotype 1 patients. Our aim was to investigate this approach in genotype 4 patients. METHODS: Viral load was measured in 46 patients before and 24 h after 10 megaunits (MU) IFN-alpha2b, and before and during 2 weeks of daily 5 MU IFN-alpha2b administration. Thereafter, patients received 48 weeks combination therapy with either 180 microg PEG-IFN-alpha2a/week (n=33), 1.5 microg/kg PEG-IFN-alpha2b/week (n=7) or 5 MU IFN-alpha2b/2 days (n=6), along with 1-1.2g RBV/day. For prediction analysis the largest group (PEG-IFN-alpha2a) was evaluated only. RESULTS: Median 24 h log10 change after 10 MU IFN-alpha2b was 1.15 (range 0.08-2.48) and after 5 MU IFN-alpha2b was 0.81 (-0.12-2.22; P<0.0001). Log10 changes after 2 weeks on 5 MU IFN-alpha2b daily and 24 h after 10 MU were the best predictors of early virological response (defined by negativity of a standard qualitative PCR) to PEG-IFN-alpha2a/RBV combination therapy (area under curve [AUC]=0.97; P<0.001, receiver operating characteristics), 24 h log10 change after 10 MU was the best predictor of sustained virological response (SVR; AUC=0.91, P=0.001). CONCLUSION: As in genotype 1 patients, there is large variation in IFN responsiveness, including the presence of resistant strains, in genotype 4 patients. A 24 h log10 change after 10 MU IFN-alpha2b is an excellent predictor of SVR on PEG-IFNalpha2a/RBV combination therapy. This test may be useful to obtain homogeneous groups for clinical studies and could help in clinical decision making.     

Impact of high‐dose interferon induction and ribavirin therapy in patients with chronic hepatitis C relapsing after or not responding to interferon monotherapy

Background/aims: Initial high‐dose interferon‐α induction therapy in combination with ribavirin improves sustained response rates in treatment‐naïve patients. This prospective, randomized, controlled study tested whether non‐responders or relapsers to interferon monotherapy also benefit from induction therapy. Methods: Patients with chronic hepatitis C who had not responded to (n=75) or relapsed (n=80) after previous interferon therapy were randomized to receive three different interferon doses during the first 14 weeks of therapy (A: 10 MU IntronA®/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; B:5 MU/d for 14 weeks; C: 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. All patients received 1–1.2 g ribavirin/day throughout the whole study. Results: The rates of viral clearance at any time on treatment were similar in all groups. Sustained response rates were also not different among the groups in interferon nonresponders (A 32%, B 29%, C 31%) and relapsers (A 64%, B 68%, C 71%), respectively, as well as in patients with different genotypes. As expected, sustained response rates were higher in patients with genotype non‐1 than in those with genotype 1. Conclusion: High‐dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers.     

A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa-2a in hepatitis C virus genotypes 2 and 3

We compared the efficacy and tolerability of 24 weeks of treatment with ribavirin 800 mg/day (group A) or 400 mg/day (group B) plus peginterferon alfa-2a 180 mug/week in treatment-naive patients infected with hepatitis C virus (HCV) genotype 2 or 3. A total of 97 of 141 patients randomized to group A (68.8%, 95% confidence interval [CI] 60.5%-76.3%) and 90 of 141 patients randomized to group B (63.8; 95% CI 55.3%-71.7%) achieved a sustained virological response, defined as undetectable serum HCV RNA at the end of untreated follow-up (week 48). Among patients infected with genotype 3, the rate of sustained virological response was 67.5% (95% CI 58.4%-75.6%) in group A and 63.9% (95% CI 54.7%-72.4%) in group B, and among patients infected with genotype 2, the rate of sustained virological response was 77.8% (95% CI 54.2%-93.6%) in group A and 55.6% (95% CI 38.4%-83.7%) in group B. Relapse rates in the 2 treatment groups were similar (17% in group A and 20% in group B). The incidence of adverse events, laboratory abnormalities, and dose reductions was similar in the 2 treatment groups. CONCLUSION: The results suggest that when administered for 24 weeks with peginterferon alfa-2a, ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV genotype 3.     

Development of insulin-dependent diabetes mellitus in a patient with chronic hepatitis C during therapy with interferon-alpha

Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis. It has been associated with various forms of autoimmune disease, e.g. autoimmune hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mellitus. Further, an increase of insulin resistance and development of non-insulin-dependent diabetes mellitus has been described after treatment with IFN-alpha. Several studies have investigated the induction of different autoimmune markers by IFN-alpha, but only few specified patients who developed insulin-dependent diabetes mellitus. We report the case of a 37-year-old man with chronic hepatitis C who was treated with IFN-alpha plus ribavirin. Thirty weeks after the start of treatment, the patient developed insulin-dependent diabetes mellitus and therapy was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of diabetes mellitus, the C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive family history for type 2 diabetes. Several autoimmune markers were investigated before, during and 6 months after withdrawal of antiviral treatment. High titres of glutamic acid decarboxylase (GAD) antibodies were present before therapy. A significant increase in titres of islet cell antibodies, parietal cell antibodies and sperm antibodies was present after 14 weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha therapy, these antibodies had significantly decreased whereas GAD antibodies remained unchanged. There was no clinical sign of any other autoimmune disease. Our data show that, in patients with a predisposition to insulin-dependent diabetes mellitus, the disease may become manifest as a side-effect during therapy with IFN-alpha. Several pathogenetic factors may be involved in this process, and, in addition to IFN-alpha, hepatitis C itself may induce autoimmune mechanisms. We conclude that screening for autoantibodies specific for type 1 diabetes should be performed before the start of IFN-alpha treatment. In patients found to be at increased risk of developing diabetes mellitus type 1, monitoring of titres of these antibodies during therapy could help to assess the individual risk-benefit ratio of IFN-alpha treatment.     

Langzeitergebnisse nach Hartmann-Operationen

Zusammenfassung. Hintergrund: Die Hartmann-Operation, die von der Mehrzahl der Chirurgen als Standardeingriff bei perforierten Colonprozessen und Vorliegen einer Peritonitis angesehen wird, wurde in den letzten Jahren wiederholt kritisiert. Von den Befürwortern einzeitiger Therapieverfahren wurden ihr schlechte postoperative (hohe Morbidit?t und Letalit?t) und Langzeitergebnisse (geringe Reanastomosierungsraten) vorgeworfen. Das Ziel unserer Untersuchung war es, zu analysieren, inwieweit diese Kritik aus der Sicht der Langzeitergebnisse gerechtfertigt ist. Methode: Bei 103 Patienten erfolgte in den Jahren 1982–1997 eine Hartmann-Operation wegen perforierter Colonprozesse. In 63 % waren entzündliche Erkrankungen Ursache der Dickdarmkomplikationen. Der mittlere Mannheimer Peritonitis Index (MPI) der Patienten betrug 19. 17 Patienten verstarben postoperativ (Letalit?t 16,5 %). 69 Patienten (80 %) wurden nach einem medianen Intervall von 122 Tagen reanastomosiert (Komplikationsrate: 6 %, Letalit?t: 0). Bei der Nachuntersuchung wurden der Allgemeinzustand, ?nderungen der Wohnsituation, k?rperliche Beschwerden und die Lebensqualit?t der Patienten erhoben. Ergebnisse: Daten von 96 % aller Patienten (83) konnten erhoben werden. Das mediane Nachbeobachtungsintervall betrug 75 Monate. Elf Patienten waren zwischenzeitlich verstorben, 72 konnten nachuntersucht werden; 86 % bezeichneten ihre Lebensqualit?t als gut oder sehr gut, nur 11 % klagten über eine starke Einschr?nkung ihrer Leistungsf?higkeit. Die Gruppen von rekonstruierten und nicht reanastomosierten Patienten zeigten dabei keine Unterschiede. Anastomosenstenosen traten in 7 % (alle nach maschineller Anastomose) auf. Schlu?folgerung: Unsere Analyse zeigte für die Hartmann-Operation gute Langzeitergebnisse. Ein gro?er Anteil der Patienten (80 %) kann zu einem sp?teren Zeitpunkt rekonstruiert werden; die postoperative Morbidit?t (6 %) und Letalit?t (0 %) dieser Eingriffe ist gering. Die überwiegende Anzahl der Patienten (86 %) bezeichnet ihre Lebensqualit?t als gut oder sehr gut, wobei sich die Gruppen der reanastomosierten und nicht rekonstruierten Patienten nicht unterschieden.      

Complications after surgery for necrotising pancreatitis: risk factors and prognosis.

OBJECTIVE: To evaluate risk factors, results of treatment, and prognostic influence of complications on survival from acute necrotising pancreatitis. DESIGN: Retrospective study of prospectively collected data. SETTING: Tertiary referral centre, Austria. SUBJECTS: 100 consecutive patients operated on for necrotising pancreatitis confirmed by dynamic angio-computed tomography from 1988-1997. INTERVENTIONS: 77 patients were operated on acutely followed by open management, and in 23 the operations were delayed. MAIN OUTCOME MEASURES: Morbidity, mortality, factors predisposing to complications, prognostic effect of complications on survival. RESULTS: Acute operations, alcoholic origin, APACHE II scores of > or = 10 on admission, and organ dysfunction on admission were independent factors that predisposed patients to complications. Colonic necrosis (n = 17) bleeding (n = 12) and intestinal fistulisation (n = 10) predominated. The overall mortality of complicated pancreatic necrosis was higher among patients admitted with surgical complications than in those who were not, but not significantly so (12/33 compared with 7/44 p = 0.06). Colonic necrosis (mortality 53%, relative risk: 2.45, p = 0.01), however, seemed to be of prognostic relevance. CONCLUSIONS: Complications are common in severe necrotising pancreatitis leading to organ dysfunction and need for acute operations. Colonic necrosis is an independent prognostic factor for survival.     

Structured management strategy based on the Gastro-oesophageal Reflux Disease (GERD) Questionnaire (GerdQ) vs. usual primary care for GERD: pooled analysis of five cluster-randomised European studies

Background: Response to treatment among primary care patients with gastro‐oesophageal disease (GERD) is variable. Aim: The GERD Management Project (GMP) evaluated the effectiveness of a structured management approach to GERD vs. standard treatment (usual care). Methods: Data from five cluster‐randomised clinical trials in adult primary care patients with symptoms of GERD were pooled. The structured pathway was based on the self‐administered GERD Questionnaire (GerdQ) and was compared with standard treatment. Results: 1734 patients were enrolled (structured treatment, n = 834; standard treatment, n = 900). The difference in the mean GerdQ score change from baseline favoured the structured pathway (?0.61; 95% CI: ?0.88, ?0.34; p < 0.001). The odds ratio for an indication for treatment revision at the end of follow‐up (structured vs. standard treatment) was 0.39 (95% CI: 0.29, 0.52; p = 0.001). Conclusions: Management of primary care patients with GERD can be improved by systematic stratification of patients using a patient management tool such as the GerdQ.