Real-life data on the impact of successful downstaging in patients with hepatocellular carcinoma: A Dutch Multicenter Study.

Patients with Barcelona Clinic Liver Cancer intermediate stage hepatocellular carcinoma (HCC) theoretically are an excellent group to consider downstaging using locoregional therapy (LRT) since they do not have extrahepatic spread or vascular invasion. Once successful, this can change the treatment strategy from palliative to curative intention. Although downstaging therapy is suggested in guidelines, it is still not widely accepted. Moreover, studies on downstaging are mainly performed in high-incidence HCC countries. Therefore, our aim was to gain insight in therapeutic strategies in patients with intermediate stage HCC and their impact on intention-to-treat survival in a real-life setting in a low-incidence HCC country. We retrospectively analyzed data from the national Dutch HCC registry. From this database, consisting of 1409 patients with a diagnosis of HCC between 2005-2013 in 5 Dutch tertiary referral centers, we identified 165 patients with intermediate stage HCC. Out of these patients, 63 (38%) were not offered LRT, whereas 102 (62%) did receive LRT. Subsequently, 50 (49%) of the 102 patients who received LRT were successfully downstaged. Eleven patients (22% of successfully downstaged patients) eventually underwent liver transplantation. Cox regression analysis showed that a lower MELD score, an AFP value <100 ng/ml, successful downstaging and liver transplantation (all ≤p = 0.01) were positively associated to overall survival. In conclusion, our results demonstrate that LRT is not routinely offered to intermediate stage HCC patients in the Netherlands. Nevertheless, we showed that patients with intermediate stage HCC who are successfully downstaged have a survival benefit compared to those who were not.

Trends in incidence, diagnosis, treatment and survival of hepatocellular carcinoma in a low-incidence country: Data from the Netherlands in the period 2009-2016.

OBJECTIVE: Evaluation of the trends in incidence, diagnostics, treatment and survival of patients with hepatocellular carcinoma (HCC) in the Netherlands. METHOD: Data regarding incidence, diagnostics, primary treatment and survival of patients with HCC in the period 2009-2016 were obtained from the Netherlands Cancer Registry. Trends in incidence, diagnostics, various treatment modalities (except liver transplantation, due to inaccurate data) and regional treatment preferences were analysed. Survival was evaluated using Kaplan-Meier curves and multivariable Cox proportional hazard regression modelling. RESULTS: In the period of 2009-2016, 3838 patients were diagnosed with HCC. A distinct decrease in the percentage of patients who underwent tumour biopsy was observed (from 51% in 2009-2010 to 42% in 2015-2016). Percentage of patients who underwent cancer treatment increased markedly (from 49% in 2009-2010 to 57% in 2015-2016), mainly because of an increasing use of resection and ablation. The number of hospitals where resections were performed or sorafenib treatment prescribed decreased slightly. The number of hospitals sporadically (<1 ablation per year) performing ablations increased. There were significant differences between regions in the application of resection, ablation and transarterial chemoembolisation /radioembolisation (p < 0.05 after 'case mix'-correction). One-, 3- and 5-year survival of patients with HCC significantly improved in the studied period. Receiving cancer treatment was associated with increased survival, whereas increasing age and an advanced tumour stage were both associated with decreased survival. CONCLUSION: From 2009 to 2016, patients with hepatocellular carcinoma more often received cancer treatment and their survival improved. There were significant differences in types of treatment between various regions.

Endoscopic management of gastrointestinal motility disorders - part 1: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

ESGE recommends the use of a graded pneumatic dilation protocol in achalasia, starting with a 30-mm dilation and followed by a 35-mm dilation at a planned interval of 2 - 4 weeks, with a subsequent 40-mm dilation when there is insufficient relief, over both a single balloon dilation procedure or the use of a larger balloon from the outset.Strong recommendation, high quality of evidence, level of agreement 100 %.ESGE recommends being cautious in treating spastic motility disorders other than achalasia with peroral endoscopic myotomy (POEM).Strong recommendation, very low quality of evidence, level of agreement 87.5 %.ESGE recommends against the routine use of botulinum toxin injections to treat patients with non-achalasia hypercontractile esophageal motility disorders (Jackhammer esophagus, distal esophageal spasm). However, if, in individual patients, endoscopic injection of botulinum toxin is chosen, ESGE recommends performing injections into four quadrants of the lower esophageal sphincter and in the lower third of the esophagus.Strong recommendation, low quality of evidence, level of agreement 78.6 %.ESGE recommends that endoscopic pylorus-directed therapy should be considered only in patients with symptoms suggestive of gastroparesis in combination with objective proof of delayed gastric emptying using a validated test, and only when medical therapy has failed.Strong recommendation, very low quality of evidence, level of agreement 100 %.ESGE recommends against the use of botulinum toxin injection in the treatment of unselected patients with gastroparesis. Strong recommendation, high quality of evidence, level of agreement 92.9 %.ESGE recommends consideration of gastric peroral endoscopic myotomy (G-POEM) in carefully selected patients only, because it is an emerging procedure with limited data on effectiveness, safety, and durability. G-POEM should be performed in expert centers only, preferably in the context of a clinical trial.Strong recommendation, low quality of evidence, level of agreement 100 %.

Endoscopic management of gastrointestinal motility disorders - part 2: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

ESGE suggests flexible endoscopic treatment over open surgical treatment as first-line therapy for patients with a symptomatic Zenker's diverticulum of any size.Weak recommendation, low quality of evidence, level of agreement 100 %.ESGE recommends that emerging treatments for Zenker's diverticulum, such as Zenker's peroral endoscopic myotomy (Z-POEM) and tunneling, be considered as experimental; these treatments should be offered in a research setting only.Strong recommendation, low quality of evidence, level of agreement 100 %.ESGE recommends against the widespread clinical use of transoral incisionless fundoplication (TIF) as an alternative to proton pump inhibitor (PPI) therapy or antireflux surgery in the treatment of gastroesophageal reflux disease (GERD), because of the lack of data on the long-term outcomes, the inferiority of TIF to fundoplication, and its modest efficacy in only highly selected patients. TIF may have a role for patients with mild GERD who are not willing to take PPIs or undergo antireflux surgery.Strong recommendation, moderate quality of evidence, level of agreement 92.8 %.ESGE recommends against the use of the Medigus ultrasonic surgical endostapler (MUSE) in clinical practice because of insufficient data showing its effectiveness and safety in patients with GERD. MUSE should be used in clinical trials only.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends against the use of antireflux mucosectomy (ARMS) in routine clinical practice in the treatment of GERD because of the lack of data and its potential complications.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends endoscopic cecostomy only after conservative management with medical therapies or retrograde lavage has failed.Strong recommendation, low quality evidence, level of agreement 93.3 %.ESGE recommends fixing the cecum to the abdominal wall at three points (using T-anchors, a double-needle suturing device, or laparoscopic fixation) to prevent leaks and infectious adverse events, whatever percutaneous endoscopic cecostomy method is used.Strong recommendation, very low quality evidence, level of agreement 86.7 %.ESGE recommends considering endoscopic decompression of the colon in patients with Ogilvie's syndrome that is not improving with conservative treatment.Strong recommendation, low quality evidence, level of agreement 93.8 %.ESGE recommends prompt endoscopic decompression if the cecal diameter is > 12 cm and if the Ogilvie's syndrome exists for a duration of longer than 4 - 6 days.Strong recommendation, low quality evidence, level of agreement 87.5 %.

Hepatocellular carcinoma in noncirrhotic livers is associated with steatosis rather than steatohepatitis: potential implications for pathogenesis.

OBJECTIVE: The risk of hepatocellular carcinoma (HCC) is increased in patients with metabolic syndrome (MS), possibly related to nonalcoholic fatty liver disease (NAFLD). As histological features of NAFLD may regress in cirrhosis, we compared steatosis versus steatohepatitis in the nontumoral liver of noncirrhotic HCC patients. PATIENTS AND METHODS: A retrospective clinicopathological analysis was carried out in 91 noncirrhotic HCC patients. Patients were divided into three subgroups: that is, patients with: (1) MS without other risk factors for underlying liver disease, (2) no underlying risk factors, or (3) other risk factors (with or without MS). The NAFLD activity score (NAS) less than 3 was classified as no steatohepatitis, NAS 3-4 as borderline steatohepatitis, and NAS 5 or more as definite steatohepatitis. RESULTS: Eleven (12%) patients had MS without other risk factors (group 1). In the nontumoral liver, significant steatosis (≥5% of hepatocytes) was generally present (in 10/11 patients), with mild lobular inflammation and absence of ballooning in most cases. Absence of steatohepatitis, borderline steatohepatitis, and definite steatohepatitis were found in 55, 45, and 0% of cases, respectively. In groups 2 and 3, significant steatosis was frequently present (in 16/37 and 21/43 patients, respectively). Absence of steatohepatitis, borderline steatohepatitis, and definite steatohepatitis were found in 84, 16, and 0% of cases (group 2), respectively, in 77, 23, and 0% of cases (group 3). CONCLUSION: In noncirrhotic HCC patients, histological steatosis was frequently present, whereas overt steatohepatitis did not occur. These findings may be relevant for HCC pathogenesis in NAFLD.

Clinical impact of five large-scale screening projects for chronic hepatitis B in Chinese migrants in the Netherlands.

BACKGROUND & AIMS: In low-endemic countries it is debated whether first-generation migrants should be screened for chronic hepatitis B infection. We describe the clinical impact of five large-scale Dutch screening projects for hepatitis B in first-generation Chinese migrants. METHODS: Between 2009 and 2013 five independent outreach screening projects for hepatitis B targeting first-generation Chinese migrants were conducted in five main Dutch regions. To explore the relevance of our screening we defined clinical impact as the presence of an indication for: (i) antiviral therapy, (ii) strict follow-up because of high hepatitis B DNA levels and/or (iii) surveillance for hepatocellular carcinoma. RESULTS: In total, 4423 persons participated in the projects of whom 6.0% (n = 264) were HBsAg positive. One hundred and twenty-nine newly diagnosed HBsAg-positive patients were analysed in specialist care. Among these patients prevalence of cirrhosis was 6.9% and antiviral therapy for hepatitis B was started in 32 patients (25%). In patients without a treatment indication, strict follow-up because of high hepatitis B DNA levels and/or surveillance for hepatocellular carcinoma was considered indicated in 64 patients (50%). CONCLUSIONS: In our screening project in first-generation Chinese migrants, antiviral treatment, strict follow-up because of high hepatitis B DNA levels and/or surveillance for hepatocellular carcinoma were considered indicated in three of four analysed HBsAg-positive patients. These data show that detection of hepatitis B in Chinese migrants can have considerable impact on patient care.

Adherence to ribavirin in chronic hepatitis C patients on antiviral treatment: Results from a randomized controlled trial using real-time medication monitoring.

BACKGROUND AND OBJECTIVE: Adherence is essential in antiviral therapy for chronic hepatitis C. We investigated the effect of real-time medication monitoring on adherence to ribavirin. METHODS: In this randomized controlled trial, patients in the intervention group received a medication dispenser that monitored ribavirin intake real-time during 24 weeks PEG-interferon/ribavirin±boceprevir or telaprevir. Patients in the control group received standard-of-care. Adherence was also measured by pill count. RESULTS: Seventy-two patients were assigned to either intervention (n=35) or control groups (n=37). Median adherence by pill count was 96% (range: 43%-100%) with 30 (94%) of patients exhibiting≥80% adherence. Perfect adherence (i.e. 100%) was similar in intervention and control groups: 22 (85%) vs. 15 (75%) (P=0.47). Adherences by real-time medication monitoring and by pill count did not correlate (R=0.19, P=0.36). No predictors of poor adherence could be identified. Ribavirin trough levels after 8 weeks (median: 2.4 vs. 2.7mg/L, P=0.30) and 24 weeks (median: 3.0 vs. 3.0mg/L, P=0.69), and virological responses did not differ between intervention and control groups. CONCLUSIONS: Adherence to ribavirin during PEG-interferon containing therapy in chronic hepatitis C is high. Real-time medication monitoring did not influence adherence to ribavirin, plasma ribavirin levels or virological responses.

Hepatocellular carcinoma in cirrhotic versus noncirrhotic livers: results from a large cohort in the Netherlands.

OBJECTIVES: Hepatocellular carcinoma (HCC) usually occurs in patients with cirrhosis, but can also develop in noncirrhotic livers. In the present study we explored associated risk factors for HCC without cirrhosis and compared patient and tumor characteristics and outcomes in HCC patients with and without underlying cirrhosis. METHODS: Patients with HCC diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated. Patients were categorized according to the presence of cirrhosis on the basis of histology or combined radiological and laboratory features. RESULTS: In total, 19% of the 1221 HCC patients had no underlying cirrhosis. Noncirrhotic HCC patients were more likely to be female and to have nonalcoholic fatty liver disease or no risk factors for underlying liver disease, and less likely to have hepatitis C virus or alcohol-related liver disease than did cirrhotic HCC patients. HCCs in noncirrhotic livers were more often unifocal (67 vs. 48%), but tumor size was significantly larger (8 vs. 4 cm). Despite the larger tumors, more patients underwent resection (50 vs. 10%) and overall survival was significantly better than in cirrhotics. In multivariate analyses, absence of cirrhosis [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.38-0.63] and presence of hepatitis B (HR 0.68, 95% CI 0.51-0.91) were independent predictors for lower mortality, whereas hepatitis C virus was associated with higher mortality (HR 1.32, 95% CI 1.01-1.65). CONCLUSION: HCC without cirrhosis was strongly associated with female sex and presence of nonalcoholic fatty liver disease or no risk factors for underlying liver disease. In absence of cirrhosis, resections were more often performed, with better survival despite larger tumor size.

Effects of preventive versus "on-demand" nutritional support on paid labour productivity, physical exercise and performance status during PEG-interferon-containing treatment for hepatitis C.

BACKGROUND AND OBJECTIVE: Deterioration of nutritional status during PEG-interferon containing therapy for chronic hepatitis C can be ameliorated by preventive nutritional support. We aimed to explore whether such support also affects paid labour productivity, physical exercise and performance status. METHODS: In this prospective randomized controlled trial (J Hepatol 2012;57:1069-75), 53 patients with chronic hepatitis C had been allocated to "on demand" support (n=26: nutritional intervention if weight loss>5%) or preventive support (n=27: regular dietary advice plus energy- and protein-rich evening snack) during PEG-interferon-containing therapy. Paid labour productivity, physical exercise and performance status were evaluated at baseline, after 24 and (if applicable) after 48 weeks of treatment. RESULTS: At baseline, 46% of patients performed paid labour and 62% performed some kind of physical exercise. Furthermore, most patients were able to carry out normal activity with only minor symptoms of disease (mean Karnofsky performance score: 94). Decreases of paid labour productivity (-21% vs. -70%, P=0.003), physical exercise activity (-43% vs. -87%, P=0.005) and Karnofsky performance scores (-12% vs. -24%, P<0.001) were less in the preventive than in "on demand" group after 24 weeks of treatment. Effects of preventive nutritional support were even more pronounced after 48 weeks. CONCLUSIONS: Preventive nutritional support markedly ameliorates decreases of paid labour productivity, physical exercise and performance status during PEG-interferon-containing treatment for chronic hepatitis C.

Surveillance for hepatocellular carcinoma is associated with increased survival: Results from a large cohort in the Netherlands.

BACKGROUND & AIMS: Effectiveness of surveillance for hepatocellular carcinoma is controversial. We here explore its effects in "real life" clinical practice. METHODS: Patients with hepatocellular carcinoma diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated. Surveillance was defined as ⩾2 screening tests during three preceding years and at least one radiologic imaging test within 18 months before diagnosis. RESULTS: 295 (27%) of 1074 cases underwent surveillance. Median time interval between last negative radiologic imaging and hepatocellular carcinoma diagnosis was 7.5 months. In the surveillance group, cirrhosis (97% vs. 60%, p<0.001) and viral hepatitis were more frequent, and non-alcoholic fatty liver disease or absence of risk factors less frequent. In case of surveillance, tumor size was significantly smaller (2.7 vs. 6.0 cm), with lower alpha-fetoprotein levels (16 vs. 44 µg/L), earlier tumor stage (BCLC 0 and A combined: 61% vs. 21%) and resection/transplantation (34% vs. 25%) or radiofrequency ablation (23% vs. 7%) more often applied, with significantly higher 1-, 3-, and 5-year survival rates. Survival benefit by surveillance remained significant after adjustment for lead-time bias based on assumed tumor doubling time of 90 days, but not with doubling time of ⩾120 days. In multivariate analysis, surveillance was an independent predictor for mortality (for interval ⩽9 respectively >9 months: adjusted HRs 0.51 and 0.50, 95% confidence intervals: 0.39-0.67 and 0.37-0.69). CONCLUSIONS: Surveillance for hepatocellular carcinoma was associated with smaller tumor size, earlier tumor stage, with an impact on therapeutic strategy and was an independent predictor of survival.

Survival in relation to hospital type after resection or sorafenib treatment for hepatocellular carcinoma in The Netherlands.

BACKGROUND AND OBJECTIVE: Despite an increase in recent years, hepatocellular carcinoma remains uncommon in the Netherlands. The aim of the current study is to explore potential effects of hospital type and volume on outcomes after resection or sorafenib in patients with hepatocellular carcinoma. METHODS: Initial treatment and survival of patients with hepatocellular carcinoma diagnosed in the period 2005-2011 were based on data of the Netherlands Cancer Registration. Potential risk factors (including hospital type and volume) for 30-days postoperative and long-term mortality in patients who underwent resection and in patients treated with sorafenib were evaluated by uni- and multivariate analyses. RESULTS: In the period 2005-2011, 2402 patients were diagnosed with hepatocellular carcinoma: 12% received resection and 9% sorafenib. Postoperative mortality was higher in non-university hospitals (13% versus 4%; P=0.01). Resection in non-university hospitals was associated with higher postoperative mortality (odds ratio 3.38, 95% confidence interval 1.37-10.68) and long-term mortality (hazard ratio 1.21, 95% confidence interval 1.04-1.40). Sorafenib treatment in non-university hospitals was also associated with higher long-term mortality (hazard ratio 1.39, 95% confidence interval 1.06-1.82). Hospital volume was not independent predictor for outcome. CONCLUSION: In low incidence countries, outcome after resection or sorafenib for hepatocellular carcinoma may differ between various hospital types.

No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long-term follow-up.

BACKGROUND AND AIMS: Data on risk of hepatocellular carcinoma (HCC) in patients with Wilson disease are scarce. We determine HCC risk in a well-defined cohort of Wilson patients. METHODS: All patients with a confirmed diagnosis of Wilson disease (Leipzig score ≥ 4) in three Dutch university referral hospitals were included in this retrospective cohort study. End of follow-up was defined as date of diagnosis of HCC, liver transplantation, death, or last available hospital visit. Also, a meta-analysis was performed to determine incidence and mortality rate of HCC in Wilson disease based on all published cohorts. RESULTS: In total, 130 patients with Wilson disease were followed during a median follow-up of 15 years (range 0.1-51.2). At baseline, cirrhosis was present in 74 patients (57% of total: 64% compensated, and 36% decompensated). At end of follow-up, liver disease severity was improved, stable or deteriorated in 20%, 46%, and 24% of all cases (10% unknown), respectively. Two patients developed HCC (one despite excellent decoppering after 50 years follow-up, the other with newly diagnosed Wilson disease). Estimated annual HCC risk for all patients was 0.09% (95% confidence interval [CI]: 0.01-0.28). Subgroup analysis in cirrhotic patients revealed an annual HCC risk of 0.14% (95% CI: 0.02-0.46). The meta-analysis showed an annual HCC risk of 0.04% (95% CI: 0.01-0.10) and HCC mortality rate of 2.6/10 000 person-years (95% CI: 0.7-7.0). CONCLUSIONS: Even in case of cirrhosis, HCC risk is low in Wilson disease. Our data do not support regular HCC surveillance in Wilson disease.

[Diagnostics and treatment of hepatocellular carcinoma: trends in the Netherlands in the period 2003-2011]. / Hepatocellulair carcinoom: diagnostiek en behandeling: trends in Nederland in de periode 2003-2011.

OBJECTIVE: To evaluate trends in the distribution of care for patients with hepatocellular carcinoma (HCC) in the past decade. DESIGN: Retrospective study. METHOD: We collected data on diagnostic testing and initial treatment of patients with HCC in the period 2003-2011 from the Dutch Cancer Registry. RESULTS: In the period 2003-2011, 2915 patients were diagnosed with HCC. The proportion of patients given palliative treatment increased significantly, whereas the proportion of patients treated by resection remained stable (approximately 10%). Tumour biopsies were performed in virtually all hospitals. Despite a significant decrease seen in the period studied, tumour biopsy was still performed in more than 50% of cases. The number of hospitals where any treatment was performed increased significantly (from 33% to 62% of all hospitals) and the contribution of treatments in academic hospitals decreased significantly (from 83% to 75%). Transarterial chemoembolization (TACE), radiofrequency ablation (RFA) and resection were mainly performed in academic hospitals (99%, 95% and 79% respectively), whereas about half of the initial sorafenib treatments were given in non-academic hospitals. Only in a few academic hospitals were a minimum of five resections performed annually and (only during the last three years of the period studied) were a minimum of five patients started on sorafenib annually. Significant differences existed between regions in the use of RFA or TACE - both p < 0.001, after case-mix correction. CONCLUSION: In the past decade there was no trend towards centralization of diagnostic testing and treatments for patients with HCC.

Surveillance for hepatocellular carcinoma in chronic liver disease: evidence and controversies.

Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis, hemochromatosis, primary biliary cirrhosis and non-alcoholic steatohepatitis. Especially cirrhotic patients are at risk of HCC and regular surveillance could enable early detection and therapy, with potentially improved outcome. We here summarize existing evidence for surveillance including ultrasound, other radiological modalities and various serum biomarkers, and current international guideline recommendations for surveillance. Ultrasound and α-fetoprotein (alone or in combination) are most frequently used for surveillance, but their sensitivities and specificities are still far from perfect, and evidence for surveillance remains weak and controversial. Various other potential surveillance tools have been tested, including serum markers as des-carboxyprothrombin, lectin-bound α-fetoprotein, and (most recently) circulating TIE2-expressing monocytes, and radiological investigations such as computed tomography-scan or magnetic resonance imaging-scan. Although early results appear promising, these tools have generally been tested in diagnostic rather than surveillance setting, and in most cases, no detailed information is available on their cost-effectiveness. For the near future, it remains important to define those patients with highest risk of HCC and most benefit from surveillance, and to restrict surveillance to these categories.

Role of dietary factors in survival and mortality in colorectal cancer: a systematic review.

The role of dietary factors in the outcome of colorectal cancer (CRC) has been the subject of many studies, but results are inconclusive. Presented here are the results of a systematic review of studies published on dietary factors and CRC outcome in the English literature between March 2002 and March 2012. Studies were subdivided into survival studies in CRC patients and CRC mortality studies in the general population. Sixteen of the 636 studies identified--5 on survival and 11 on mortality--met the predefined inclusion criteria. No consistent association between individual dietary components and CRC outcome was detected in the survival studies. In the mortality studies, an association between meat intake and increased CRC mortality was found in two ecologic studies; however, two prospective cohort studies did not confirm this association. An inverse association between cereal intake and CRC mortality was found in two ecologic studies. In conclusion, published studies investigating dietary factors and outcome in CRC are heterogeneous in design and findings. No dietary component was conclusively and consistently associated with survival in CRC patients. The results of mortality studies seem to indicate that meat intake has an adverse effect on CRC mortality, while cereal intake may be protective.

Long-term follow up in patients with gastroesophageal reflux disease with specific emphasis on reflux symptoms, use of anti-reflux medication and anti-reflux surgery outcome: a retrospective study.

BACKGROUND: Various treatment modalities are currently being used in patients with gastroesophageal reflux disease (GERD); however, long-term outcome is not clear. The aim is to evaluate long-term results of GERD treatments with regard to reflux symptoms, use of anti-reflux medication and anti-reflux surgery outcome. METHODS: Patients who had undergone 24-h pH monitoring for reflux symptoms between January 2002 and March 2012 were invited to fill out the Reflux Disease Questionnaire (RDQ) and a general questionnaire. Patients with and without anti-reflux surgery were compared using multiple linear and logistic regression models. RESULTS: In total, 1027 of 2190 included patients (47%) returned the questionnaires. After exclusion due to predefined criteria, 477 patients were analyzed. Median total RDQ score was 18 points (10.2% symptom-free) in the conservative group (n = 304) and 10 points (31.2% symptom-free) in the surgical group (n = 173) after a mean follow up of 5.1 years. Daily proton pomp inhibitor (PPI) use was higher in the conservative group than in the surgical group (80.9% vs. 51.4%, p = 0.000). Linear regression analysis showed an association between RDQ scores and anti-reflux surgery (ß = -5.477, p = 0.001) and male gender (ß = -4.306, p = 0.006). Logistic regression analyses showed that daily PPI use was lower in patients who underwent anti-reflux surgery (odds ratio [OR] = 0.24, p = 0.000), while it increased with age (OR = 1.03, p = 0.000). CONCLUSIONS: There is still a high prevalence of typical reflux symptoms and daily PPI use in GERD patients after >5 years of follow up. Male patients and patients who had undergone anti-reflux surgery were more often asymptomatic. Daily PPI use was lower after anti-reflux surgery, while it increased with age.