Werner Weiss

Sex-Specific Prevalence of Adenomas, Advanced Adenomas, and Colorectal Cancer in Individuals Undergoing Screening Colonoscopy

CONTEXT Although some studies have shown that men are at greater age-specific risk for advanced colorectal neoplasia than women, the age for referring patients to screening colonoscopy is independent of sex and usually recommended to be 50 years. OBJECTIVE To determine and compare the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas (AAs), and colorectal carcinomas (CRCs) for different age groups in men and women. DESIGN, SETTING, AND PATIENTS Cohort study of 44,350 participants in a national screening colonoscopy program over a 4-year period (2007 to 2010) in Austria. MAIN OUTCOME MEASURES Prevalence and NNS of adenomas, AAs, and CRCs in different age groups for men and women. RESULTS The median ages were 60.7 years (interquartile range [IQR], 54.5-67.5 years) for women and 60.6 years (IQR, 54.3-67.6 years) for men, and the sex ratio was nearly identical (51.0% [22,598] vs 49.0% [21,572]). Adenomas were found in 19.7% of individuals screened (95% CI, 19.3%-20.1%; n = 8743), AAs in 6.3% (95% CI, 6.1%-6.5%; n = 2781), and CRCs in 1.1% (95% CI, 1.0%-1.2%; n = 491); NNS were 5.1 (95% CI, 5.0-5.2), 15.9 (95% CI, 15.4-16.5), and 90.9 (95% CI, 83.3-100.0), respectively. Male sex was significantly associated with a higher prevalence of adenomas (24.9% [95% CI, 24.3%-25.4%] vs 14.8% [95% CI, 14.3%-15.2%]; P < .001; unadjusted odds ratio [OR], 1.9 [95% CI, 1.8-2.0]), AAs (8.0% [95% CI, 7.6%-8.3%] vs 4.7% [95% CI, 4.4%-4.9%]; P < .001; unadjusted OR, 1.8 [95% CI, 1.6-1.9]), and CRCs (1.5% [95% CI, 1.3%-1.7%] vs 0.7% [95% CI, 0.6%-0.9%]; P < .001; unadjusted OR, 2.1 [95% CI, 1.7-2.5]). The prevalence of AAs in 50- to 54-year-old individuals was 5.0% (95% CI, 4.4%-5.6%) in men but 2.9% (95% CI, 2.5%-3.4%) in women (adjusted P = .001); the NNS in men was 20 (95% CI, 17.8-22.6) vs 34 in women (95% CI, 29.1-40; adjusted P = .001). There was no statistical significance between the prevalence and NNS of AAs in men aged 45 to 49 years compared with women aged 55 to 59 years (3.8% [95% CI, 2.3%-6.1%] vs 3.9% [95% CI, 3.3%-4.5%] and 26.1 [95% CI, 16.5-44.4] vs 26 [95% CI, 22.5-30.2]; P = .99). CONCLUSION Among a cohort of Austrian individuals undergoing screening colonoscopy, the prevalence and NNS of AAs were comparable between men aged 45 to 49 years and women aged 55 to 59 years.

High-grade dysplasia and invasive carcinoma in colorectal adenomas: a multivariate analysis of the impact of adenoma and patient characteristics.

Background and aims Most colorectal carcinomas develop from preformed adenomas, but only a minority of adenomas undergo malignant transformation. The clinical significance of polyps of size < 0.5 cm is controversial. The primary goal of this study was to assess the independent risk factors of adenoma and patient characteristics associated with advanced pathological features (APF; i.e. high-grade dysplasia or invasive carcinoma) in colorectal adenomas. A secondary goal was to assess the malignant potential of adenomas with a diameter of < 0.5 cm. Patients and methods Patients who underwent total colonoscopy at our Medical Department between 1978 and 1996 and had at least one colorectal adenoma were considered for this study. Patients with a history of colorectal cancer, prior polypectomy or colorectal surgery were excluded. A total of 7590 adenomas removed from 4216 patients were included in this analysis. Logistic regression analysis was used to study the impact of different adenoma and patient characteristics on the risk of APF. Results Size proved to be the most important risk factor for APF. The percentage of adenomas with APF was 3.4%, 13.5% and 38.5% for adenomas of diameter < 0.5 cm, 0.5–1 cm and > 1 cm, respectively. Villous or tubulovillous histology, left-sided location and age ⩾ 60 years were also associated with APF, whereas sex and number of adenomas had no significant impact. Logistic regression analysis revealed that the risk of an adenoma containing APF was best described by a model incorporating the factors size, location, age, and the age by histology interaction. In the class of adenomas with diameter < 0.5 cm, no invasive carcinoma was found, but 3.4% of adenomas had high-grade dysplasia. Conclusions The risk of a colorectal adenoma containing APF can be estimated only by a complex model taking into account several adenoma and patient characteristics. Size, histological type, location and age are independent risk factors for APF in colorectal adenomas. As a considerable percentage of adenomas with diameter < 0.5 cm contain high-grade dysplasia, the clinical conclusion from our study is that all adenomas, including those with diameter < 0.5 cm, should be removed whenever possible.

The pancreas as a site of granulomatous inflammation in Crohn's disease

Several reports on the occurrence of pancreatic dysfunction complicating Crohns disease have been published during the past few years. Nevertheless, the pathogenesis of these disorders remains controversial. In this report, we describe a patient presenting with extrahepatic cholestasis and a mass in the head of the pancreas. Histological examination showed a granulomatous inflammation caused by Crohns disease involving the stomach, the duodenum, and the head of the pancreas, clearly showing that the pancreas can also be a localization of Crohns disease. Granulomatous inflammation could be an important factor in the pathogenesis of pancreatic dysfunction occurring in association with Crohns disease.

Sedation in Screening Colonoscopy: Impact on Quality Indicators And Complications

OBJECTIVES:Quality indicators including cecal intubation rate (CIR) and adenoma detection rate (ADR) are established. Sex differences of quality indicators are observed, but the influence of sedation has not been investigated so far. The objective of this study is to assess the impact of sedation on quality indicators, including CIR and ADR, according to sex.METHODS:We analyzed data of 52,506 screening colonoscopies performed by 196 endoscopists between November 2007 and April 2011 according to the Austrian “quality management for colon cancer prevention” program.RESULTS:Sedation did not affect polyp detection rate (women P=0.7972, men P=0.3711) or ADR for both sexes (women P=0.2773, men P=0.8676). ADR was not significantly influenced by sedation (P=0.1272), but by age and sex (both P<0.0001), when the executing endoscopist was considered. Although women were more often sedated than men (90.70 vs. 81.83%; P<0.0001), CIR was slightly lower in women than in men (94.69 vs. 96.58%; P<0.0001). Sedation improved the CIR in women by 2.95% (94.96 vs. 92.01%; P<0.0001), whereas in men it was just by 1.28% (96.81 vs. 95.53%; P<0.0001). Sedated women only reached the CIR of unsedated men (94.96 vs. 95.53%; P=0.1005). Accounting for the intra-observer influence of the endoscopist, the overall CIR was influenced by the interaction of sex and age (P=0.0049), but not by sedation (P=0.1435).CONCLUSIONS:Sedation does not increase adenoma or polyp detection, although it leads to an increase in CIR in men and women. This effect is more pronounced in women, yet CIR of men remains higher compared with women. Quality indicators are mainly influenced by the patients age, sex, and the endoscopists’ individual performance, rather than the endoscopists’ subspeciality or procedural experience.

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

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.

Eradication of Helicobacter pylori by a 1-week course of famotidine, amoxicillin and clarithromycin

Objectives The combination of a proton pump inhibitor (PPI) such as omeprazole with amoxicillin and clarithromycin constitutes one of the most effective treatments for the eradication of Helicobacter pylori. Nevertheless, the mechanisms of interaction between these drugs remain unclear. It has been shown that minimal inhibitory concentration values of both antibiotics are considerably lower at neutral pH levels than in an acid environment. Further, omeprazole possesses bacteriostatic activity. To evaluate the significance of these mechanisms we replaced omeprazole with famotidine, a drug which only suppresses acid production, but has no intrinsic antimicrobial activity. Methods We evaluated the efficacy of a 1-week course of famotidine 80 mg b.i.d., amoxicillin 1000 mg b.i.d. and clarithromycin 500 mg b.i.d. in a pilot study (20 patients), and then confirmed our results in a larger replication study (87 patients). A total of 107 patients with H. pylori-associated duodenal ulcer (n = 54), gastric ulcer (n = 14) or non-ulcer dyspepsia (n = 39) were included. Endoscopy was performed at baseline and 4–6 weeks after discontinuation of treatment H. pylori status was assessed by the urease test and histology. Results H. pylori was successfully eradicated in 94 of 104 patients who completed the study (90.4%; Cl 95%, 83.0–95.3%). By intention-to-treat analysis, the eradication rate was 87.9% (Cl 95%, 80.1–93.4%). Ulcer healing was observed in 98.1% of duodenal ulcers and 92.9% of gastric ulcers (based on per-protocol analysis). Mild side effects that did not require termination of treatment were reported by seven patients (6.7%). Conclusion A 1-week course of famotidine, amoxicillin and clarithromycin is a highly effective, simple and safe eradication regimen. Our data indicate that acid suppression is the crucial mechanism by which the activity of amoxicillin and clarithromycin against H. pylori is enhanced, whereas additional antimicrobial activity or other specific effects of PPIs seem to be less important.

Course of platelet counts in cirrhotic patients after implantation of a transjugular intrahepatic portosystemic shunt - a prospective, controlled study

BACKGROUND/AIMS The pathogenesis of thrombocytopenia associated with advanced liver disease is still controversial. To study the impact of portal decompression on this hematologic complication, we conducted a prospective, controlled study to compare the course of platelet counts in patients after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) with matched controls without shunts. METHODS Fifty-five TIPS patients and 110 controls matched for age, sex, Child-Pugh class, etiology of liver disease and baseline platelet count were included, and followed for 1 year. Follow-up visits were scheduled after 1 month, after 3 months, and at 3-month intervals thereafter. RESULTS Nonparametric Mann-Whitney U-tests revealed significantly higher platelet counts for TIPS patients as compared to controls from the 1st through the 12th month (p<0.01). During the study period, the median platelet count of TIPS patients increased by 19.7%, from 104.0/nl (IR: 68.0) to 124.5/nl (IR: 41.0). In contrast, during the same period the median platelet count of controls decreased by 17.1%, from 102.5/nl (IR: 66.0) to 85.0/nl (IR: 67.5). In the group of cases with baseline platelet counts < or =100/nl, platelet counts had increased by at least 25% at month 12 in 65% of TIPS patients, but in only 5% of controls (p<0.001). However, normalization of platelet counts, i.e. > or =150/nl, was not achieved in any case. Neither the portosystemic pressure gradient after TIPS implantation, nor the percentage of portosystemic pressure gradient reduction during the procedure was predictive of platelet response. CONCLUSIONS TIPS implantation increases platelet counts significantly. However, portal hypertension is clearly not the only mechanism contributing to thrombocytopenia in advanced liver disease.

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° grade rotation in the three dimensional mode. The chosen matrix was 128×128×16, 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.

Clinical outcome two years after implantation of a transjugular intrahepatic portosystemic shunt for recurrent variceal bleeding

Objective: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a relatively new therapy for variceal bleeding. The aim of this study was to assess clinical course 2 years after TIPS procedure. Design: The study was designed as a prospective, uncontrolled cohort study. Methods: Forty‐six patients who underwent successful TIPS implantation were followed prospectively by clinical examinations, duplex sonography and portal venography. Mean follow‐up in surviving patients was 24.1 ±9.0 months. Results: The cumulative rate of survival was 80.4% at 1 year and 70.2% at 2 years. The cumulative rebleeding rate was 12.4% at 1 year and 21.3% at 2 years. The mortality rate of episodes of variceal rebleeding was 22.2%. Variceal rebleeding was associated with shunt abnormalities, and successful shunt revision resulted in control of the bleeding. The cumulative incidence of shunt stenosis or occlusion was 41.2% at 1 year and 54.9% at 2 years. Of those patients without shunt abnormalities after 1 year, 23.3% developed shunt stenosis or occlusion during the second year after TIPS procedure. Shunt revision was successful in 96.6% of cases. Secondary patency rate was 88.1% after 2 years. Conclusion: Successful TIPS implantation results in a low rate of morbidity and mortality from variceal rebleeding over 2 years. TIPS creation in combination with careful follow‐up examinations represents an effective long‐term treatment of recurrent variceal bleeding. Even in patients in whom no shunt abnormality is detected during the first year, routine duplex follow‐up examinations should be continued at 3‐month intervals.

High quality of screening colonoscopy in Austria is not dependent on endoscopist specialty or setting

BACKGROUND AND STUDY AIM International studies have shown differences in the outcome of screening colonoscopies related to the endoscopists specialty and setting of colonoscopy. The aim of this study was to investigate the impact of these two factors on quality parameters for screening colonoscopy in a quality-assured screening program. METHODS Adenoma detection rate (ADR), cecal intubation rate (CIR), polypectomy rate, flat polyp detection rate, carcinoma detection rate, sedation rate, complication rates, and other parameters of 59 901 screening colonoscopies performed by 178 endoscopists were analyzed in relation to specialty (35 gastroenterologists: 10 066 colonoscopies [16.8 %]; 84 nongastroenterologists: 26 271 colonoscopies [43.9 %]; 59 surgeons: 23 564 [39.3 %]), and setting (hospital: 12 580 [21.6 %] colonoscopies; office: 45 781 [78.4 %] colonoscopies). RESULTS The overall ADR was 20.5 % and the CIR was 95.6 %. The ADR did not show any statistical significance, either in relation to specialty or to setting. A significant difference in the CIR was found between hospital-based and office-based internists (98.5 % vs. 96.8 %, respectively; P  = 0.0005; odds ratio [OR] 2.2, 95 % confidence interval [CI] 1.4 - 3.4). Hospital-based internists had a significantly higher flat polyp detection rate (7.5 % vs. 4.1 %; P  = 0.02; OR 1.9, 95 %CI 1.1 - 3.2) and a significantly lower carcinoma detection rate (0.4 % vs. 0.6 %; P  = 0.03; OR 0.7, 95 %CI 0.5 - 1.0) compared with office-based internists. Complication rates were significantly lower among surgeons than among internists (0.1 % vs. 0.2 %; P  = 0.03; OR 0.5, 95 %CI 0.3 - 1.0). CONCLUSION Endoscopists participating in the Austrian quality assurance program offered high quality screening colonoscopy regardless of their specialty and setting. The implementation of a standardized quality program is therefore a decisive factor in quality improvement of screening colonoscopy.