Eruption of Metastatic Paraganglioma After Successful Therapy with 177Lu/90Y-DOTATOC and 177Lu-DOTATATE.

ABSTRACT: Metastatic paraganglioma treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been introduced as a novel management option for metastatic neuroendocrine tumors demonstrating safety, efficacy, and increased quality of life. We present two cases of marked progression of metastatic paraganglioma following initial partial response to PRRT. Given their positivity on 68Ga-DOTATATE PET/CT and 111In-octreotide SPECT, they underwent PRRT. Imaging following treatment revealed significant improvement in size and intensity, with some foci nearly completely resolved in one patient, and disease regression with a decrease in the number and size of bone and liver lesions in the second patient. Within months, repeat imaging in both patients revealed extensive metastatic disease with new lesions, which eventually lead to their deaths. The mechanism for rapid disease progression after partial response is not well understood, although it could be related to initially high Ki-67 levels or 18F-FDG PET/CT SUVmax values. However, naturally rapid disease progression despite PRRT response cannot be excluded. This finding warrants the importance of proper patient counseling along with early and accurate pre-PRRT assessment, taking into consideration the above potential risk factors for therapy response in order to personalize treatment regimens and achieve maximum patient benefit. CLINICALTRIALSGOV IDENTIFIER: NCT00004847.

Ancillary investigations to diagnose parkinsonism: a prospective clinical study.

Various ancillary investigations can assist clinicians in the differential diagnosis of patients with parkinsonism. It is unknown which test offers greatest diagnostic value in clinical practice. We included 156 consecutive patients with parkinsonism, but with an initially uncertain diagnosis. At baseline, all patients underwent extensive clinical testing and the following ancillary investigations: brain magnetic resonance imaging (MRI); (123)I-iodobenzamide single photon-emission computed tomography (IBZM-SPECT); analysis of cerebrospinal fluid (CSF); and anal sphincter electromyography (EMG). The final diagnosis was established after 3-year follow-up by two movement disorder specialists, according to international consensus criteria. We determined the diagnostic value by comparing the baseline clinical parameters and ancillary studies with the final diagnosis. Out of a potential 138 parameters, univariate analysis identified 35 parameters that discriminated Parkinson's disease (PD, n = 62) and atypical parkinsonism (AP, n = 94), with AUC of 0.55-0.81. Stepwise logistic regression showed that the combination of tandem gait, axial UPDRS subscore, slow saccadic eye movements and dysphagia yielded an AUC of 0.93, adjusted for optimism. The combination of tandem gait and axial UDPRS subscore yielded an AUC of 0.90. None of the ancillary investigations alone or in combination with clinical testing improved this clinically based diagnostic accuracy, not even in a subgroup of patients with the greatest diagnostic uncertainty at baseline. Our study demonstrates that a comprehensive set of clinical tests provides good accuracy to differentiate PD from AP. Our results also suggest that routine MRI, IBZM-SPECT, CSF analysis and anal sphincter EMG do not improve this diagnostic accuracy. Future work should evaluate the possible diagnostic value of more advanced diagnostic tests.

Which patient-related factors determine self-perceived patient adherence to prescribed dyspepsia medication?

Patient adherence to medical treatment for dyspepsia is disappointing, whereas adherence is crucial for a proper evaluation of treatment. This prospective study used elements of the Integrated Change Model and Weiner's Attribution Theory to describe patients' important cognitions and their interrelationships regarding self-perceived adherence to short-term medical treatment for dyspepsia. Patient questionnaires measured the predictors before treatment and self-perceived adherence after treatment. Approximately one-quarter of the patients indicated that they were non-adherent (n = 347). Univariate and multiple linear regression analyses revealed several significant predictors that explained 44% of the variance in self-perceived adherence. Patients with a low educational level, patients who claimed to regularly forget their medication in general, patients with a low self-efficacy or a low intention were less likely to be adherent. These results may indicate targets for interventions designed to improve adherence to medical treatment for dyspepsia. For instance, asking about expected difficulties in taking acid suppressants (e.g. forgetfulness or medication use at weekends) and making action plans to overcome these difficulties (e.g. using reminders) may result in improved adherence rates. Such an approach may reach a substantial number of patients since one in five patients in our study experienced some difficulties in taking medication.

Seven-day PPI-triple therapy with levofloxacin is very effective for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori infection causes lifelong gastritis and is associated with the development of peptic ulcer disease, MALT lymphoma and gastric cancer. Many patients benefit from H. pylori eradication therapy. PPI-triple therapy is recommended as initial therapy. Quadruple therapy, with a PPI, bismuth, and two antibiotics, used to be recommended as second-line therapy, but can no longer be prescribed because bismuth is no longer available. Therefore, there is an urgent need for new effective rescue therapies. Levofloxacin-based therapies were suggested as an alternative to quadruple therapy. The aim of this study is to examine the efficacy and tolerability of such a one-week therapy with levofloxacin and esomeprazole combined with either amoxicillin or clarithromycin in a Dutch population. METHODS: Between February 2005 and November 2006, 123 consecutive H. pylori positive patients were enrolled in this study. The first 59 patients were treated with esomeprazole, amoxicillin and levofloxacin (group I). The next 64 patients were treated with esomeprazole, clarithromycin, and levofloxacin (group II ). Both therapies were compared for efficacy and tolerability. RESULTS: In group I the overall (ITT) cure rate was 96% and in group II it was 93%. Minor side effects occurred in 29% of patients in group I and in 41% of patients in group II. Major side effects that warranted discontinuation of therapy occurred in two patients in group II. CONCLUSION: Seven-day triple therapy with esomeprazole, levofloxacin and either amoxicillin or clarithromycin for seven days is very effective and safe for H. pylori eradication. The combination with amoxicillin seems to be better tolerated than the combination with clarithromycin.

Measuring the severity of upper gastrointestinal complaints: does GP assessment correspond with patients' self-assessment?

BACKGROUND: Questionnaires are frequently used to measure the severity of gastrointestinal (GI) complaints. These questionnaires can either be filled out by the physicians or by the patients, but it is not clear whether these scores correspond. This study aimed to investigate the interrater agreement between physician-reported severity and patient-reported severity concerning the patients' upper GI complaints. METHODS: In a prospective observational study, the severity of eight GI complaints was registered by both patients and GPs independently on a seven-point scale (n = 316) before and after treatment with esomeprazole. Weighted kappa values for the agreement on the severity and simple kappa values for the agreement on the absence or presence of symptoms were calculated. RESULTS: The weighted kappa values ranged from 0.14 to 0.68 indicating poor to moderate agreement. The agreement on the presence or absence of symptoms was similar. Several systematic differences in scoring were found: the GPs tended to underestimate the severity of belching, nausea, early satiety, vomiting and upper and lower abdominal pain. Furthermore, the treatment effect for belching and lower abdominal pain was more often overestimated, while the treatment effect for nausea was more often underestimated by the GP. CONCLUSION: The agreement between GP and patient is low. The differences in scoring should be kept in mind when comparing physician-reported outcomes with patient-reported outcomes.

Evaluation of a gastrointestinal symptoms questionnaire.

Questionnaires are widely used instruments to monitor gastrointestinal (GI) symptoms. However, few of these questionnaires have been formally evaluated. We sought to evaluate our GI symptoms questionnaire in terms of clarity and reproducibility. Primary care patients referred for open access Helicobacter pylori urea breath testing reported GI symptoms (type+severity) and demographic information by written questionnaire. In an interview, patients gave a personal description of the meaning of the GI symptoms on the questionnaire. Patients' descriptions of GI symptoms were compared with current definitions. Symptom severity scores were compared before and after, interview versus questionnaire. Of the 45 patients included, 19 (42%) described all symptoms correctly, whereas 17 (38%) described one symptom incorrectly. None of the patients made more than three mistakes. Regurgitation was the most common incorrectly described symptom (16 patients [36%]), whereas the other individual symptoms were well explained. Symptom severities before the interview, after the interview and reported by questionnaire (mean value+/-SEM) were 2.1 +/- 0.2, 2.1 +/- 0.2, and 1.5 +/- 0.2 points on a 7-point Likert scale (0-6), respectively. Mean severity reported by interview (95% CI) was 1.4 (1.3-1.5) times higher than reported by questionnaire (P < .05). In conclusion, the GI symptom questionnaire is understandable and has good reproducibility for measuring the presence of GI symptoms, although symptom severity is consistently rated higher when reported by interview.

Helicobacter pylori antibiotic resistance in a Dutch region: trends over time.

AIM: Most patients treated for H. pylori infection receive empirical therapy based on epidemiological data of antibiotic resistance. However, previous European studies indicate that resistance patterns may be changing. Therefore, the aim of this study was to investigate the prevalence of primary clarithromycin and/or metronidazole resistant H. pylori strains over a six-year period (1997-2002) in a regional hospital. METHODS: All patients visiting Slingeland Hospital in Doetinchem, the Netherlands between 1997 and 2002 with a positive H. pylori culture were included in this study. Susceptibility to metronidazole and clarithromycin was determined by disk diffusion. RESULTS: Of the 1355 patients with an H. pylori positive culture, 1127 did not have a history of H. pylori eradication, 58 did, and for 170 this information was not available. Mean rates of primary resistance to metronidazole and clarithromycin were 14.4% (162/1125) and 1.0% (11/1123), respectively. Primary metronidazole resistance was stable throughout the study period and primary clarithromycin resistance showed a decreasing trend. Patients of foreign descent and from secondary care had a higher chance of harbouring primary metronidazole-resistant H. pylori (adjusted OR (95% CI) 1.75 (1.1 to 2.8), and 1.60 (1.1 to 2.2), respectively). Patients with failed H. pylori eradication had a higher chance of harbouring metronidazole-resistant H. pylori (43 vs 14%, p<0.0001) and clarithromycin-resistantH. pylori (5.3 vs 1.0%, p=0.004) than untreated patients. CONCLUSION: Primary metronidazole resistance is stableat a low level, while primary clarithromycin resistance isvirtually absent in the eastern part of the Netherlands.Therefore, triple therapy with a proton pump inhibitor,clarithromycin and amoxicillin can remain the empiricaltreatment of choice in the Netherlands.

[Low prevalence of metronidazole- and clarithomycin-resistant Helicobacter pylori in the 's-Hertogenbosch region, 1998-2003]. / Lage prevalentie van metronidazol- en claritromycineresistente Helicobacter pylori in de regio 's-Hertogenbosch, 1998-2003.

OBJECTIVE: To measure the prevalence of metronidazole- or clarithromycin-resistant Helicobacter pylori. DESIGN. Retrospective. METHOD: All positive H. pylori cultures with known susceptibility to metronidazole or clarithromycin between 1998 and 2003 were selected from the database of the Microbiology Laboratory in 's-Hertogenbosch, the Netherlands. Resistance to clarithromycin and metronidazole was determined using the E-test with cut-off minimum inhibitory concentrations of > or = 2 microg/ml and > or = 8 microg/ml, respectively. RESULTS: Of the 960 cultures with known metronidazole susceptibility, 135 (14%) were resistant. Of the 959 cultures with known clarithromycin susceptibility, 26 (3%) were resistant. The percentages of resistant cultures were higher in women than in men (17% versus 12% and 4% versus 2%, respectively). There was no relationship between age and resistance. Over the course of the study period, resistance to metronidazole decreased slightly, whereas resistance to clarithromycin increased slightly. CONCLUSION: Prevalence of metronidazole- and clarithromycin-resistant H. pylori strains in the 's-Hertogenbosch region was so low that the combination of a proton pump inhibitor, clarithromycin and amoxicillin can be used in patients with H. pylori infection without first determining susceptibility.

Meta-analysis: the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication.

BACKGROUND: There is much debate about the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication. The few studies investigating the influence of pre-treatment on triple and quadruple therapies did not find differences in eradication rates. However, the high eradication rates make it difficult to study factors associated with therapy failure in small populations. In order to overcome this problem we performed a meta-analysis. METHODS: The literature was searched in order to identify randomized clinical trials comparing modern triple/quadruple therapies for H. pylori eradication without pre-treatment with a proton pump inhibitor with exactly the same regimen with pre-treatment. The overall risk difference (with - without pre-treatment) was calculated by pooling the risk differences of the individual studies weighted by the inverse of their variances. RESULTS: Nine studies, investigating a total of 773 patients, were identified. There was considerable variation regarding therapy regimen and duration. Pooled eradication rates were 81.3% (312 of 384) for patients with pre-treatment and 81.2% (316 of 389) for patients without pre-treatment. The (weighted) overall risk difference was 0.1% (95% CI: -5%; 5%). CONCLUSION: Pre-treatment with a proton pump inhibitor does not influence H. pylori eradication.

Meta-analysis: the diagnostic value of alarm symptoms for upper gastrointestinal malignancy.

BACKGROUND: With the advent of empirical treatment strategies for patients with dyspeptic symptoms, it becomes increasingly important to select patients with a high risk of having cancer for immediate endoscopy. Usually alarming symptoms are used for this matter, but their diagnostic value is by no means clear. AIM: To investigate the diagnostic value of alarm symptoms for upper gastrointestinal malignancy. METHODS: Meta-analysis of studies describing prevalence of alarm symptoms in patients with and without endoscopically verified upper gastrointestinal malignancy were identified through a Medline search. The prevalence, pooled sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: About 17 case studies and nine cohort studies were selected. The mean prevalence of gastrointestinal malignancies in the cohort studies was 2.8% of 16,161 patients. Five cohort studies indicated that 25% of the patients diagnosed with upper gastrointestinal malignancy had no alarm symptoms. The pooled sensitivities of individual alarm symptoms varied from 9 to 41%, the pooled positive predictive value ranged from 4.6 to 7.9%, and was 5.9% for 'having any alarm symptom'. The pooled negative predictive value was 99.4% for 'having any alarm symptom'. CONCLUSION: The risk of upper gastrointestinal malignancy in any individual without alarm symptoms is very low, but approximately one in four patients with upper gastrointestinal cancer have no alarm symptoms at the time of diagnosis.

The influence of pretreatment on cure rates of Helicobacter pylori eradication.

BACKGROUND: Many patients treated for H. pylori infection have been taking a proton pump inhibitor beforehand. There is conflicting evidence whether pretreatment influences the efficacy of H. pylori eradication. The aim of this study was to investigate the influence of pretreatment on cure rates of H. pylori eradication. METHODS: Patients with H. pylori positive peptic ulcer disease or functional dyspepsia were treated with two-day quadruple therapy (lansoprazole 30 mg twice daily, and colloidal bismuth subcitrate 120 mg, tetracycline 250 mg and metronidazole 250 mg, all eight times a day). Patients were randomised to receive either three-day pretreatment with lansoprazole 30 mg twice daily or no pretreatment. H. pylori was diagnosed using CLO, histology and culture. RESULTS: Twenty-five (66%) of 38 patients with pretreatment and 32 (84%) of 38 patients without pretreatment were cured (p=0.06). After adjustment for diagnosis, smoking status and metronidazole resistance the influence of pretreatment became slightly less pronounced (OR 0.44, 95% CI 0.1-1.7). Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication than smokers and patients with functional dyspepsia, respectively (adjusted odds ratios: 4.79 (1.2-19) and 4.32 (1.0-18)). CONCLUSIONS: This two-day quadruple therapy reached an overall cure rate of 75%. Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication. Three-day pretreatment with a proton pump inhibitor may decrease cure rates of this two-day quadruple therapy.

Gastric acid-suppressive therapy and community-acquired respiratory infections.

BACKGROUND: Bacteria and viruses have been detected in the stomach of patients during acid-suppressive therapy. AIM: To investigate whether subjects using acid-suppressive drugs more often develop community-acquired respiratory infections when compared to those who do not use acid-suppressive drugs. METHODS: 700 study subjects were recruited during a single week in December 2002. Information on the prevalence of clinical manifestations of infections and complications in the preceding month was assessed by questionnaire. Furthermore, subjects were asked to report antibiotic therapy and physician visits related to possible infection. RESULTS: Questionnaires were returned by 405 subjects (58%). Consumption of acid-suppressive drugs was reported by 91 individuals, of whom 79 used proton-pump inhibitors (20%) and 12 H2-receptor antagonists (3%). Overall, 101 (25%) responders reported clinical manifestations of respiratory infection in the preceding month. Subjects using acid-suppressive drugs were 2.34 times [95% confidence interval (CI) 1.4-4.1] more likely to have clinical manifestations of infection than individuals not using acid-suppressive drugs. Subjects using acid-suppressive drugs visited a physician 3.72 times more often (95% CI 2.1-6.8) for an infection and received antibiotic therapy 4.19 times more often (95% CI 2.2-8.1) in comparison to individuals not using acid-suppressive drugs. CONCLUSIONS: Subjects using acid-suppressive drugs more often reported community-acquired respiratory infections in comparison to those who did not use acid-suppressive drugs.